Caveolae: mining little caves for new cancer targets

Caveolae exist at cell surfaces as caveolin-coated invaginations that perform transport and signalling functions influencing cell growth, apoptosis, angiogenesis and transvascular exchange. Caveolin could constitute a key switch in tumour development through its function as a tumour suppressor and as a promoter of metastasis, chemoresistance and survival. Targeting of drugs and gene vectors to tissue-specific proteins in caveolae allows selective delivery into vascular endothelial cells in vivo and might even improve direct access to solid-tumour cells. Therefore, caveolae seem to be rich in potential targets for cancer imaging and therapeutics.

[1]  P. Oh,et al.  NEM inhibits transcytosis, endocytosis, and capillary permeability: implication of caveolae fusion in endothelia. , 1995, The American journal of physiology.

[2]  P. Carmeliet,et al.  Angiogenesis in cancer and other diseases , 2000, Nature.

[3]  V. J. Venema,et al.  VEGF-induced permeability increase is mediated by caveolae. , 1999, Investigative ophthalmology & visual science.

[4]  Pranav Sharma,et al.  GPI-anchored proteins are delivered to recycling endosomes via a distinct cdc42-regulated, clathrin-independent pinocytic pathway. , 2002, Developmental cell.

[5]  Richard G. W. Anderson,et al.  Caveolin, a protein component of caveolae membrane coats , 1992, Cell.

[6]  R. G. Anderson,et al.  Early effects of PP60v‐src kinase activation on caveolae , 1998, Journal of Cellular Biochemistry.

[7]  D. Sacks,et al.  Reciprocal Regulation of Endothelial Nitric-oxide Synthase by Ca2+-Calmodulin and Caveolin* , 1997, The Journal of Biological Chemistry.

[8]  Young-Mi Go,et al.  Plasma Membrane Cholesterol Is a Key Molecule in Shear Stress-dependent Activation of Extracellular Signal-regulated Kinase* , 1998, The Journal of Biological Chemistry.

[9]  H. Dvorak,et al.  Caveolae and Vesiculo-Vacuolar Organelles in Bovine Capillary Endothelial Cells Cultured with VPF/VEGF on Floating Matrigel-collagen Gels , 1999, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[10]  I. Herman,et al.  Mechanisms of normal and tumor-derived angiogenesis. , 2002, American journal of physiology. Cell physiology.

[11]  Jan E. Schnitzer,et al.  Role of GTP Hydrolysis in Fission of Caveolae Directly from Plasma Membranes , 1996, Science.

[12]  P. Verkade,et al.  Induction of Caveolae in the Apical Plasma Membrane of Madin-Darby Canine Kidney Cells , 2000, The Journal of cell biology.

[13]  J. Frøkjaer-Jensen,et al.  The endothelial vesicle system in cryofixed frog mesenteric capillaries analysed by ultrathin serial sectioning. , 1991, Journal of electron microscopy technique.

[14]  Jan E Schnitzer,et al.  Tumor cell growth inhibition by caveolin re-expression in human breast cancer cells , 1998, Oncogene.

[15]  W. Zundel,et al.  Caveolin 1-Mediated Regulation of Receptor Tyrosine Kinase-Associated Phosphatidylinositol 3-Kinase Activity by Ceramide , 2000, Molecular and Cellular Biology.

[16]  Ken Jacobson,et al.  A Role for Lipid Shells in Targeting Proteins to Caveolae, Rafts, and Other Lipid Domains , 2002, Science.

[17]  F. Burrows,et al.  Vascular targeting--a new approach to the therapy of solid tumors. , 1994, Pharmacology & therapeutics.

[18]  R. Parton,et al.  Detergent-insoluble glycolipid microdomains in lymphocytes in the absence of caveolae. , 1994, The Journal of biological chemistry.

[19]  J. Glenney Tyrosine phosphorylation of a 22-kDa protein is correlated with transformation by Rous sarcoma virus. , 1989, The Journal of biological chemistry.

[20]  R. Munford,et al.  Bacterial lipopolysaccharide can enter monocytes via two CD14-dependent pathways. , 1998, Journal of immunology.

[21]  G. Garcı́a-Cardeña,et al.  Endothelial Nitric Oxide Synthase Is Regulated by Tyrosine Phosphorylation and Interacts with Caveolin-1* , 1996, The Journal of Biological Chemistry.

[22]  G. Keller,et al.  Endocytosis of glycophospholipid‐anchored and transmembrane forms of CD4 by different endocytic pathways. , 1992, The EMBO journal.

[23]  J. Schnitzer gp60 is an albumin-binding glycoprotein expressed by continuous endothelium involved in albumin transcytosis. , 1992, The American journal of physiology.

[24]  J. Schnitzer,et al.  Caveolae: from basic trafficking mechanisms to targeting transcytosis for tissue-specific drug and gene delivery in vivo. , 2001, Advanced drug delivery reviews.

[25]  Richard J. Lee,et al.  Reciprocal Regulation of Neu Tyrosine Kinase Activity and Caveolin-1 Protein Expression in Vitro and in Vivo , 1998, The Journal of Biological Chemistry.

[26]  P. Oh,et al.  Filipin-sensitive caveolae-mediated transport in endothelium: reduced transcytosis, scavenger endocytosis, and capillary permeability of select macromolecules , 1994, The Journal of cell biology.

[27]  H. Jo,et al.  Caveolin-1 regulates shear stress-dependent activation of extracellular signal-regulated kinase. , 2000, American journal of physiology. Heart and circulatory physiology.

[28]  J. E. Celis,et al.  Cell Biology: A Laboratory Handbook , 1997 .

[29]  Vladimir P. Torchilin,et al.  Biomedical aspects of drug targeting , 2002 .

[30]  P. Oh,et al.  Immunoisolation of Caveolae with High Affinity Antibody Binding to the Oligomeric Caveolin Cage , 1999, The Journal of Biological Chemistry.

[31]  A. Quest,et al.  Caveolin-1 levels are down-regulated in human colon tumors, and ectopic expression of caveolin-1 in colon carcinoma cell lines reduces cell tumorigenicity. , 2000, Cancer research.

[32]  A. Ullrich,et al.  High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis , 1993, Cell.

[33]  L. Orci,et al.  Ligands internalized through coated or noncoated invaginations follow a common intracellular pathway. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[34]  G. Christ,et al.  Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities. , 2001, The Journal of biological chemistry.

[35]  P. Conrad,et al.  Caveolin moves from caveolae to the Golgi apparatus in response to cholesterol oxidation , 1994, The Journal of cell biology.

[36]  D. Gingras,et al.  Regulation of vascular endothelial growth factor receptor-2 activity by caveolin-1 and plasma membrane cholesterol. , 2003, Molecular biology of the cell.

[37]  S. Woodman,et al.  Microvascular Hyperpermeability in Caveolin-1 (−/−) Knock-out Mice , 2002, The Journal of Biological Chemistry.

[38]  R. D. Rudic,et al.  In vivo delivery of the caveolin-1 scaffolding domain inhibits nitric oxide synthesis and reduces inflammation , 2000, Nature Medicine.

[39]  M Oshima,et al.  Loss of Apc heterozygosity and abnormal tissue building in nascent intestinal polyps in mice carrying a truncated Apc gene. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[40]  J. Schnitzer Update on the cellular and molecular basis of capillary permeability. , 1993, Trends in cardiovascular medicine.

[41]  M. Kattan,et al.  Elevated expression of caveolin is associated with prostate and breast cancer. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[42]  Charles C. Wykoff,et al.  Recombinant Expression of Caveolin-1 in Oncogenically Transformed Cells Abrogates Anchorage-independent Growth* , 1997, The Journal of Biological Chemistry.

[43]  M. Robinson,et al.  Caveolin-1 expression is associated with high-grade bladder cancer. , 2001, Urology.

[44]  I. Nabi,et al.  Distinct caveolae-mediated endocytic pathways target the Golgi apparatus and the endoplasmic reticulum , 2003, Journal of Cell Science.

[45]  Richard G. W. Anderson,et al.  Identification of caveolin-1 in lipoprotein particles secreted by exocrine cells , 1999, Nature Cell Biology.

[46]  H. Dvorak,et al.  Structure of solid tumors and their vasculature: implications for therapy with monoclonal antibodies. , 1991, Cancer cells.

[47]  G. Fiucci,et al.  Caveolin-1 inhibits anchorage-independent growth, anoikis and invasiveness in MCF-7 human breast cancer cells , 2002, Oncogene.

[48]  K. Johnson An Update. , 1984, Journal of food protection.

[49]  N. Severs,et al.  Caveolae: static inpocketings of the plasma membrane, dynamic vesicles or plain artifact? , 1988, Journal of cell science.

[50]  T Hayakawa,et al.  Invasion activating caveolin-1 mutation in human scirrhous breast cancers. , 2001, Cancer research.

[51]  M. Bitzer,et al.  Caveolin-1 Regulates Transforming Growth Factor (TGF)-β/SMAD Signaling through an Interaction with the TGF-β Type I Receptor* , 2001, The Journal of Biological Chemistry.

[52]  G. Garcı́a-Cardeña,et al.  Dissecting the Interaction between Nitric Oxide Synthase (NOS) and Caveolin , 1997, The Journal of Biological Chemistry.

[53]  B. Zetter,et al.  Angiogenesis and tumor metastasis. , 1998, Annual review of medicine.

[54]  J. Engelman,et al.  Chromosomal localization, genomic organization, and developmental expression of the murine caveolin gene family (Cav‐1, ‐2, and ‐3) , 1998, FEBS letters.

[55]  M. Stowell,et al.  Nucleotide-dependent conformational changes in dynamin: evidence for a mechanochemical molecular spring , 1999, Nature Cell Biology.

[56]  P. Oh,et al.  Targeting endothelium and its dynamic caveolae for tissue-specific transcytosis in vivo: A pathway to overcome cell barriers to drug and gene delivery , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[57]  R. Weinberg,et al.  Effects of an Rb mutation in the mouse , 1992, Nature.

[58]  D. Muckle,et al.  Intrasarcolemmal Proliferation of the VX2 Carcinoma , 1974, British Journal of Cancer.

[59]  J. Engelman,et al.  Targeted downregulation of caveolin‐1 is sufficient to drive cell transformation and hyperactivate the p42/44 MAP kinase cascade , 1998, The EMBO journal.

[60]  T. Fujimoto,et al.  GPI-anchored proteins, glycosphingolipids, and sphingomyelin are sequestered to caveolae only after crosslinking. , 1996, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[61]  G. Fiucci,et al.  Up-regulation of Caveolae and Caveolar Constituents in Multidrug-resistant Cancer Cells* , 1998, The Journal of Biological Chemistry.

[62]  T. Timme,et al.  Suppression of caveolin expression induces androgen sensitivity in metastatic androgen-insensitive mouse prostate cancer cells , 1998, Nature Medicine.

[63]  P. Oh,et al.  Rapid Mechanotransduction in Situ at the Luminal Cell Surface of Vascular Endothelium and Its Caveolae* , 1998, The Journal of Biological Chemistry.

[64]  S. Okushiba,et al.  Overexpression of caveolin‐1 in esophageal squamous cell carcinoma correlates with lymph node metastasis and pathologic stage , 2002, Cancer.

[65]  David S. Park,et al.  Caveolin-1 mutations (P132L and null) and the pathogenesis of breast cancer: caveolin-1 (P132L) behaves in a dominant-negative manner and caveolin-1 (-/-) null mice show mammary epithelial cell hyperplasia. , 2002, The American journal of pathology.

[66]  M. Dietel,et al.  Down-regulation of caveolin-1, a candidate tumor suppressor gene, in sarcomas. , 2001, The American journal of pathology.

[67]  Lucas Pelkmans,et al.  Caveolar endocytosis of simian virus 40 reveals a new two-step vesicular-transport pathway to the ER , 2001, Nature Cell Biology.

[68]  E. Vitetta,et al.  Immunotoxins: an update. , 1996, Annual review of immunology.

[69]  J. Schnitzer,et al.  Tissue-Specific Pharmacodelivery and Overcoming Key Cell Barriers in Vivo: Vascular Targeting of Caveolae , 2002 .

[70]  J. Schnitzer,et al.  Caveolae require intact VAMP for targeted transport in vascular endothelium. , 1999, American journal of physiology. Heart and circulatory physiology.

[71]  P. Oh,et al.  Aquaporin-1 in plasma membrane and caveolae provides mercury-sensitive water channels across lung endothelium. , 1996, The American journal of physiology.

[72]  T. Aoki,et al.  Tyrosine phosphorylation of caveolin-1 in the endothelium. , 1999, Experimental cell research.

[73]  B. Haraldsson,et al.  Fluid and protein fluxes across small and large pores in the microvasculature. Application of two-pore equations. , 1987, Acta physiologica Scandinavica.

[74]  J. Schnitzer Vascular targeting as a strategy for cancer therapy. , 1998, The New England journal of medicine.

[75]  L. Donehower,et al.  Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours , 1992, Nature.

[76]  I. Nabi,et al.  Localization of autocrine motility factor receptor to caveolae and clathrin-independent internalization of its ligand to smooth endoplasmic reticulum. , 1998, Molecular biology of the cell.

[77]  M. Ittmann,et al.  Secreted caveolin-1 stimulates cell survival/clonal growth and contributes to metastasis in androgen-insensitive prostate cancer. , 2001, Cancer research.

[78]  T. Wheeler,et al.  The role of caveolin-1 in androgen insensitive prostate cancer. , 2002, The Journal of urology.

[79]  Deborah A. Brown,et al.  Structure and Function of Sphingolipid- and Cholesterol-rich Membrane Rafts* , 2000, The Journal of Biological Chemistry.

[80]  L. Orci,et al.  Non-coated membrane invaginations are involved in binding and internalization of cholera and tetanus toxins , 1982, Nature.

[81]  H Ueno,et al.  The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. , 1992, Science.

[82]  M. Lisanti,et al.  Src tyrosine kinases, Galpha subunits, and H-Ras share a common membrane-anchored scaffolding protein, caveolin. Caveolin binding negatively regulates the auto-activation of Src tyrosine kinases. , 1996, The Journal of biological chemistry.

[83]  G. Fiucci,et al.  Upregulation of caveolin in multidrug resistant cancer cells: functional implications. , 2001, Advanced drug delivery reviews.

[84]  M. Bundgaard,et al.  Endothelial plasmalemmal vesicles as elements in a system of branching invaginations from the cell surface. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[85]  R K Jain,et al.  Barriers to drug delivery in solid tumors. , 1994, Scientific American.

[86]  S. Mayor,et al.  Sequestration of GPI-anchored proteins in caveolae triggered by cross-linking. , 1994, Science.

[87]  V. Puri,et al.  Clathrin-dependent and -independent internalization of plasma membrane sphingolipids initiates two Golgi targeting pathways , 2001, The Journal of cell biology.

[88]  J. Ross,et al.  Defects in caveolin-1 cause dilated cardiomyopathy and pulmonary hypertension in knockout mice , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[89]  H. Dvorak,et al.  Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. , 1983, Science.

[90]  A. Helenius,et al.  Endocytosis of simian virus 40 into the endoplasmic reticulum , 1989, The Journal of cell biology.

[91]  M. Lisanti,et al.  Caveolin-1 expression sensitizes fibroblastic and epithelial cells to apoptotic stimulation. , 2001, American journal of physiology. Cell physiology.

[92]  M Dietel,et al.  Caveolin-1 is down-regulated in human ovarian carcinoma and acts as a candidate tumor suppressor gene. , 2001, The American journal of pathology.

[93]  Roger Fan,et al.  Dynamic activation of endothelial nitric oxide synthase by Hsp90 , 1998, Nature.

[94]  M. Lisanti,et al.  Caveolin-1, a putative tumour suppressor gene. , 2001, Biochemical Society transactions.

[95]  P. Oh,et al.  Segregation of heterotrimeric G proteins in cell surface microdomains. G(q) binds caveolin to concentrate in caveolae, whereas G(i) and G(s) target lipid rafts by default. , 2001, Molecular biology of the cell.

[96]  L. Truong,et al.  Caveolin-1 expression in clinically confined human prostate cancer: a novel prognostic marker. , 1999, Cancer research.

[97]  V. Puri,et al.  Rab proteins mediate Golgi transport of caveola-internalized glycosphingolipids and correct lipid trafficking in Niemann-Pick C cells. , 2002, The Journal of clinical investigation.

[98]  N. Simionescu,et al.  Endothelial transport of macromolecules: transcytosis and endocytosis. A look from cell biology. , 1991, Cell biology reviews : CBR.

[99]  B. Zetter,et al.  Tumor interactions with the vasculature: angiogenesis and tumor metastasis. , 1990, Biochimica et biophysica acta.

[100]  David S. Park,et al.  Loss of caveolin-1 gene expression accelerates the development of dysplastic mammary lesions in tumor-prone transgenic mice. , 2003, Molecular biology of the cell.

[101]  D. Predescu,et al.  Transcytosis in the continuous endothelium of the myocardial microvasculature is inhibited by N-ethylmaleimide. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[102]  M. McNiven,et al.  Dynamin-mediated Internalization of Caveolae , 1998, The Journal of cell biology.

[103]  E. Yamada THE FINE STRUCTURE OF THE GALL BLADDER EPITHELIUM OF THE MOUSE , 1955, The Journal of biophysical and biochemical cytology.

[104]  R K Jain,et al.  Predominant role of endothelial nitric oxide synthase in vascular endothelial growth factor-induced angiogenesis and vascular permeability , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[105]  Wei Zhang,et al.  Caveolin-1 Inhibits Epidermal Growth Factor-stimulated Lamellipod Extension and Cell Migration in Metastatic Mammary Adenocarcinoma Cells (MTLn3) , 2000, The Journal of Biological Chemistry.

[106]  G. Palade,et al.  Endothelial plasmalemmal vesicles have a characteristic striped bipolar surface structure , 1985, The Journal of cell biology.

[107]  T. Timme,et al.  Caveolin-1 is regulated by c-myc and suppresses c-myc-induced apoptosis , 2000, Oncogene.

[108]  M. Lisanti,et al.  Angiogenesis Activators and Inhibitors Differentially Regulate Caveolin-1 Expression and Caveolae Formation in Vascular Endothelial Cells , 1999, The Journal of Biological Chemistry.

[109]  H. Dvorak,et al.  Pathways of Macromolecular Extravasation Across Microvascular Endothelium in Response to VPF/VEGF and Other Vasoactive Mediators , 1999, Microcirculation.

[110]  P. Oh,et al.  Endothelial Caveolae Have the Molecular Transport Machinery for Vesicle Budding, Docking, and Fusion Including VAMP, NSF, SNAP, Annexins, and GTPases (*) , 1995, The Journal of Biological Chemistry.

[111]  P. Oh,et al.  Organized Endothelial Cell Surface Signal Transduction in Caveolae Distinct from Glycosylphosphatidylinositol-anchored Protein Microdomains* , 1997, The Journal of Biological Chemistry.

[112]  Harold E. Dvorak,et al.  Vesiculo-vacuolar organelles and the regulation of venule permeability to macromolecules by vascular permeability factor, histamine, and serotonin , 1996, The Journal of experimental medicine.

[113]  C. Ren,et al.  Caveolin-1 mediates testosterone-stimulated survival/clonal growth and promotes metastatic activities in prostate cancer cells. , 2001, Cancer research.

[114]  Napoleone Ferrara,et al.  VEGF and the quest for tumour angiogenesis factors , 2002, Nature Reviews Cancer.

[115]  V. Speights,et al.  Hypermethylation of the caveolin‐1 gene promoter in prostate cancer , 2001, The Prostate.

[116]  George Reid,et al.  Analysis of the CAVEOLIN-1 gene at human chromosome 7q31.1 in primary tumours and tumour-derived cell lines , 1999, Oncogene.

[117]  Richard G. W. Anderson,et al.  Localization of Platelet-derived Growth Factor-stimulated Phosphorylation Cascade to Caveolae (*) , 1996, The Journal of Biological Chemistry.

[118]  M. Deckert,et al.  Endocytosis of GPI-anchored proteins in human lymphocytes: role of glycolipid-based domains, actin cytoskeleton, and protein kinases , 1996, The Journal of cell biology.

[119]  L. Thornell,et al.  Placental alkaline phosphatase, a GPI-anchored protein, is clustered in clathrin-coated vesicles. , 1992, Biochemical and biophysical research communications.

[120]  K. Alitalo,et al.  Vascular endothelial growth factor is induced in response to transforming growth factor-beta in fibroblastic and epithelial cells. , 1994, The Journal of biological chemistry.

[121]  M. Drab,et al.  Loss of Caveolae, Vascular Dysfunction, and Pulmonary Defects in Caveolin-1 Gene-Disrupted Mice , 2001, Science.

[122]  P. Oh,et al.  In Situ Flow Activates Endothelial Nitric Oxide Synthase in Luminal Caveolae of Endothelium with Rapid Caveolin Dissociation and Calmodulin Association* , 1998, The Journal of Biological Chemistry.

[123]  D. Hanahan,et al.  Induction of angiogenesis during the transition from hyperplasia to neoplasia , 1989, Nature.

[124]  P. Oh,et al.  Separation of caveolae from associated microdomains of GPI-anchored proteins , 1995, Science.

[125]  P. Oh,et al.  Dynamin at the Neck of Caveolae Mediates Their Budding to Form Transport Vesicles by GTP-driven Fission from the Plasma Membrane of Endothelium , 1998, The Journal of cell biology.

[126]  V. Ullrich,et al.  Colocalization prostacyclin (PGI2) synthase--caveolin-1 in endothelial cells and new roles for PGI2 in angiogenesis. , 2001, Experimental cell research.

[127]  David S. Park,et al.  Caveolin-1 Expression Enhances Endothelial Capillary Tubule Formation* , 2002, The Journal of Biological Chemistry.

[128]  G. Bloom,et al.  Caveolin cycles between plasma membrane caveolae and the Golgi complex by microtubule-dependent and microtubule-independent steps , 1995, The Journal of cell biology.

[129]  F. Wieland,et al.  VIP21/caveolin is a cholesterol-binding protein. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[130]  D. Harris,et al.  Glycolipid-anchored proteins in neuroblastoma cells form detergent- resistant complexes without caveolin , 1995, The Journal of cell biology.

[131]  D. Baltimore,et al.  Reduction of caveolin and caveolae in oncogenically transformed cells. , 1995, Proceedings of the National Academy of Sciences of the United States of America.