Heparan sulfate proteoglycans and cancer

Heparan sulfate proteoglycans (HSPGs) are widely distributed in mammalian tissues and involved in a number of processes related to malignancy. They are composed of a core protein to which chains of the glycosaminoglycan, heparan sulfate (HS), are attached. The existence of various classes of core protein, in addition to highly polymorphic HS chains, creates a superfamily of macromolecules with considerable diversity of structure and function. HSPGs interact with many proteins including growth factors, chemokines and structural proteins of the extracellular matrix to influence cell growth, differentiation, and the cellular response to the environment. The recent identification of two inherited syndromes that are associated with an increased cancer risk, and caused by mutations in HSPG-related genes, has intensified interest in these molecules. This review describes our current understanding of HSPGs in cancer and highlights new possibilities for therapeutic control. © 2001 Cancer Research Campaign http://www.bjcancer.com

[1]  M. J. Stanley,et al.  Syndecan-1 expression is induced in the stroma of infiltrating breast carcinoma. , 1999, American journal of clinical pathology.

[2]  H. Kitagawa,et al.  The Tumor Suppressor EXT-like Gene EXTL2 Encodes an α1, 4-N-Acetylhexosaminyltransferase That TransfersN-Acetylgalactosamine and N-Acetylglucosamine to the Common Glycosaminoglycan-Protein Linkage Region , 1999, The Journal of Biological Chemistry.

[3]  S. Selleck Proteoglycans and pattern formation: sugar biochemistry meets developmental genetics. , 2000, Trends in genetics : TIG.

[4]  L. Strong,et al.  Hereditary multiple exostosis and chondrosarcoma: linkage to chromosome II and loss of heterozygosity for EXT-linked markers on chromosomes II and 8. , 1995, American journal of human genetics.

[5]  D. Schlessinger,et al.  Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome , 1996, Nature Genetics.

[6]  J. Fryns,et al.  Mutational analysis of the GPC3/GPC4 glypican gene cluster on Xq26 in patients with Simpson-Golabi-Behmel syndrome: identification of loss-of-function mutations in the GPC3 gene. , 2000, Human molecular genetics.

[7]  T. Murakami,et al.  Altered Proliferative and Metastatic Potential Associated with Increased Expression of Syndecan-1 , 1998, Tumor Biology.

[8]  M. Götte,et al.  Functions of cell surface heparan sulfate proteoglycans. , 1999, Annual review of biochemistry.

[9]  G. Jayson,et al.  Heparan Sulfate Undergoes Specific Structural Changes during the Progression from Human Colon Adenoma to Carcinoma in Vitro * , 1998, The Journal of Biological Chemistry.

[10]  A. Berchuck,et al.  Loss of heterozygosity at chromosome segment Xq25‐26.1 in advanced human ovarian carcinomas , 1997, Genes, chromosomes & cancer.

[11]  S. Jhanwar,et al.  Expression of GPC3, an X-linked recessive overgrowth gene, is silenced in malignant mesothelioma , 2000, Oncogene.

[12]  W. Skarnes,et al.  glypican-3 controls cellular responses to Bmp4 in limb patterning and skeletal development. , 2000, Developmental biology.

[13]  O. Pappo,et al.  Mammalian heparanase: Gene cloning, expression and function in tumor progression and metastasis , 1999, Nature Medicine.

[14]  Y. Yuasa,et al.  EXTL3/EXTR1 alterations in colorectal cancer cell lines. , 1999, International journal of oncology.

[15]  D. Noonan,et al.  Suppression of autocrine and paracrine functions of basic fibroblast growth factor by stable expression of perlecan antisense cDNA , 1997, Molecular and cellular biology.

[16]  C. McCormick,et al.  The Putative Tumor Suppressors EXT1 and EXT2 Are Glycosyltransferases Required for the Biosynthesis of Heparan Sulfate* , 1998, The Journal of Biological Chemistry.

[17]  M. Jalkanen,et al.  The role of syndecan-1 in malignancies. , 1996, Annals of medicine.

[18]  A. Waage,et al.  Serum syndecan-1: a new independent prognostic marker in multiple myeloma. , 2000, Blood.

[19]  M. Nugent,et al.  Antisense targeting of perlecan blocks tumor growth and angiogenesis in vivo. , 1998, The Journal of clinical investigation.

[20]  K. Nackaerts,et al.  Heparan sulfate proteoglycan expression in human lung‐cancer cells , 1997, International journal of cancer.

[21]  E. Conrad,et al.  Loss of heterozygosity in chondrosarcomas for markers linked to hereditary multiple exostoses loci on chromosomes 8 and 11. , 1995, American journal of human genetics.

[22]  M. Lyon,et al.  Heparan Sulphate: Molecular Structure and Interactions with Growth Factors and Morphogens. , 2000 .

[23]  J. Testa,et al.  OCI-5/GPC3, a Glypican Encoded by a Gene That Is Mutated in the Simpson-Golabi-Behmel Overgrowth Syndrome, Induces Apoptosis in a Cell Line–specific Manner , 1998, The Journal of cell biology.

[24]  L. Kjellén,et al.  Regulated Diversity of Heparan Sulfate* , 1998, The Journal of Biological Chemistry.

[25]  B. Weyn,et al.  Syndecan‐1 expression in malignant mesothelioma: correlation with cell differentiation, WT1 expression, and clinical outcome , 1998, The Journal of pathology.

[26]  R. Hoet,et al.  Generation and Application of Type-specific Anti-Heparan Sulfate Antibodies Using Phage Display Technology , 1998, The Journal of Biological Chemistry.

[27]  H. Friess,et al.  Syndecan‐1 expression is up‐regulated in pancreatic but not in other gastrointestinal cancers , 2000, International journal of cancer.

[28]  M. Lyon,et al.  Highly Sensitive Sequencing of the Sulfated Domains of Heparan Sulfate* , 1999, The Journal of Biological Chemistry.

[29]  A. Friedl,et al.  Differential ability of heparan sulfate proteoglycans to assemble the fibroblast growth factor receptor complex in situ , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[30]  H. Friess,et al.  The cell-surface heparan sulfate proteoglycan glypican-1 regulates growth factor action in pancreatic carcinoma cells and is overexpressed in human pancreatic cancer. , 1998, The Journal of clinical investigation.

[31]  S. Patel,et al.  Cloning and expression profiling of Hpa2, a novel mammalian heparanase family member. , 2000, Biochemical and biophysical research communications.

[32]  B. Barlogie,et al.  Syndecan-1 is a multifunctional regulator of myeloma pathobiology: control of tumor cell survival, growth, and bone cell differentiation. , 1998, Blood.

[33]  R. Hennekam Hereditary multiple exostoses. , 1991, Journal of medical genetics.

[34]  L. Solomon HEREDITARY MULTIPLE EXOSTOSIS. , 1963, American journal of human genetics.

[35]  D. Schlessinger,et al.  Frequent silencing of the GPC3 gene in ovarian cancer cell lines. , 1999, Cancer research.

[36]  D. Martindale,et al.  The putative tumour suppressor EXT1 alters the expression of cell-surface heparan sulfate , 1998, Nature Genetics.

[37]  G. Evans,et al.  EXT genes are differentially expressed in bone and cartilage during mouse embryogenesis , 2000, Developmental dynamics : an official publication of the American Association of Anatomists.

[38]  M. Bernfield,et al.  Syndecan-1 is required for Wnt-1-induced mammary tumorigenesis in mice , 2000, Nature Genetics.

[39]  J. Turnbull,et al.  Heparan Sulfate Oligosaccharides Require 6-O-Sulfation for Promotion of Basic Fibroblast Growth Factor Mitogenic Activity* , 1998, The Journal of Biological Chemistry.