The influence of CD 44 v 3v 10 on adhesion , invasion and MMP-14 expression in prostate cancer cells

The expression of certain CD44 variants has been linked with metastasis and tumour progression. In particular, high molecular weight forms of CD44 show restricted expression in tumours and may correlate with tumour development and metastasis. In this study, we examined the expression of CD44 variants in prostate cancer cell lines: the invasive PC-3 and DU-145, low invasive LNCaP, and two non-invasive prostate epithelial cell lines. PC-3 prostate cancer cells were transfected with a high molecular weight CD44 variant isoform, CD44v3-v10, isolated from non-invasive prostate epithelial cell lines. These transfected cells (PC-NIVO) were assessed using in vitro invasion, tumour-endothelial, growth, and migration assays. The expression of MMP-14 was examined using SDS-PAGE and Western blot analysis. Transfected PC-3 cells (PC-NIVO) were found to be less adherent to endothelial cells and had significantly reduced invasiveness compared to wild-type PC-3 or control cells. In addition, tumour cell adhesion to endothelial cells and invasiveness was increased after exposure to HGF/SF, and can be blocked by the presence of anti-CD44 antibodies. Further investigation revealed a reduction in the expression of MMP-14 in PC-NIVO cells, but not in PC-3 or control cells. In conclusion, non-invasive prostate epithelial cells express a high molecular weight CD44 isoform, CD44v3-v10, which may counteract the standard isoform function of CD44 by reducing adhesion and invasion of endothelium by prostate tumour cells through negation of the MMP-14 function.

[1]  Brian Seed,et al.  A lymphocyte molecule implicated in lymph node homing is a member of the cartilage link protein family , 1989, Cell.

[2]  B. Toole.  Hyaluronan and its binding proteins, the hyaladherins. , 1990, Current opinion in cell biology.

[3]  R. Cardiff,et al.  CD44v(3,8-10) is involved in cytoskeleton-mediated tumor cell migration and matrix metalloproteinase (MMP-9) association in metastatic breast cancer cells. , 1998, Journal of cellular physiology.

[4]  R. Mansel,et al.  Biphasic effects of 17‐β‐estradiol on expression of occludin and transendothelial resistance and paracellular permeability in human vascular endothelial cells , 2003, Journal of cellular physiology.

[5]  L. Bourguignon,et al.  Ankyrin-binding domain of CD44(GP85) is required for the expression of hyaluronic acid-mediated adhesion function , 1994, The Journal of cell biology.

[6]  P. Kincade,et al.  CD44 and its interaction with extracellular matrix. , 1993, Advances in immunology.

[7]  R. Timpl,et al.  Membrane-type matrix metalloproteinases 1 and 2 exhibit broad-spectrum proteolytic capacities comparable to many matrix metalloproteinases. , 1997, European journal of biochemistry.

[8]  I. Stamenkovic,et al.  Localization of matrix metalloproteinase 9 to the cell surface provides a mechanism for CD44-mediated tumor invasion. , 1999, Genes & development.

[9]  X. Chen,et al.  Hyaluronic acid-induced lymphocyte signal transduction and HA receptor (GP85/CD44)-cytoskeleton interaction. , 1993, Journal of immunology.

[10]  William,et al.  Characterization of the class III collagen receptor, a phosphorylated, transmembrane glycoprotein expressed in nucleated human cells. , 1988, The Journal of biological chemistry.

[11]  N Iida,et al.  The Cell Adhesion Molecule, GP116, Is a New CD44 Variant (ex14/v10) Involved in Hyaluronic Acid Binding and Endothelial Cell Proliferation* , 1996, The Journal of Biological Chemistry.

[12]  T. Noguchi,et al.  Immunohistochemical detection of membrane-type-1-matrix metalloproteinase in colorectal carcinoma , 2000, British Journal of Cancer.

[13]  W. Carter,et al.  Human keratinocytes express a new CD44 core protein (CD44E) as a heparan-sulfate intrinsic membrane proteoglycan with additional exons , 1991, The Journal of cell biology.

[14]  L. Bourguignon,et al.  Post-translational protein modification and expression of ankyrin-binding site(s) in GP85 (Pgp-1/CD44) and its biosynthetic precursors during T-lymphoma membrane biosynthesis. , 1991, The Journal of biological chemistry.

[15]  J. Isaacs,et al.  CD44 is a metastasis suppressor gene for prostatic cancer located on human chromosome 11p13. , 1997, Cancer research.

[16]  S. Kumar,et al.  The effect of hyaluronate and its oligosaccharides on endothelial cell proliferation and monolayer integrity. , 1989, Experimental cell research.

[17]  I. Stamenkovic,et al.  CD44 anchors the assembly of matrilysin/MMP-7 with heparin-binding epidermal growth factor precursor and ErbB4 and regulates female reproductive organ remodeling. , 2002, Genes & development.

[18]  A. D. De Marzo,et al.  CD44 and CD44v6 downregulation in clinical prostatic carcinoma: Relation to Gleason grade and cytoarchitecture , 1998, The Prostate.

[19]  J. Sleeman,et al.  How tumor cells make use of CD44. , 1998, Cell adhesion and communication.

[20]  M. Tammi,et al.  CD44 substituted with heparan sulfate and endo-beta-galactosidase-sensitive oligosaccharides: a major proteoglycan in adult human epidermis. , 1997, The Journal of investigative dermatology.

[21]  J. Woessner,et al.  Heparan Sulfate Proteoglycans as Extracellular Docking Molecules for Matrilysin (Matrix Metalloproteinase 7)* , 2000, The Journal of Biological Chemistry.

[22]  J. R. de los Toyos,et al.  Monoclonal antibodies against the CD44 [In(Lu)-related p80], and Pgp-1 antigens in man recognize the Hermes class of lymphocyte homing receptors. , 1989, Journal of immunology.

[23]  S. Jalkanen,et al.  Biochemical properties of glycoproteins involved in lymphocyte recognition of high endothelial venules in man. , 1988, Journal of immunology.

[24]  Motoharu Seiki,et al.  A matrix metalloproteinase expressed on the surface of invasive tumour cells , 1994, Nature.

[25]  P. Herrlich,et al.  The two major CD44 proteins expressed on a metastatic rat tumor cell line are derived from different splice variants: each one individually suffices to confer metastatic behavior. , 1993, Cancer research.

[26]  M. Hung,et al.  Interaction between the Adhesion Receptor, CD44, and the Oncogene Product, p185 HER2 , Promotes Human Ovarian Tumor Cell Activation* , 1997, The Journal of Biological Chemistry.

[27]  Y. Okada,et al.  Membrane‐type 1 MMP (MMP‐14) cleaves at three sites in the aggrecan interglobular domain , 1998, FEBS letters.

[28]  L. Bourguignon,et al.  Interaction of CD44 variant isoforms with hyaluronic acid and the cytoskeleton in human prostate cancer cells , 1995, Journal of cellular physiology.

[29]  I. Stamenkovic,et al.  Distinct effects of two CD44 isoforms on tumor growth in vivo , 1991, The Journal of experimental medicine.

[30]  M. Mason,et al.  Distribution and expression of CD44 isoforms and Ezrin during prostate cancer-endothelium interaction. , 2002, International journal of oncology.

[31]  Y Iwamoto,et al.  A rapid in vitro assay for quantitating the invasive potential of tumor cells. , 1987, Cancer research.

[32]  H. Mori,et al.  Membrane-Type 1 Matrix Metalloproteinase Cleaves Cd44 and Promotes Cell Migration , 2001, The Journal of cell biology.

[33]  Ronit Vogt Sionov,et al.  CD44: structure, function, and association with the malignant process. , 1997, Advances in cancer research.

[34]  B. Caterson,et al.  Membrane type 1 matrix metalloproteinase (MT1-MMP) cleaves the recombinant aggrecan substrate rAgg1mut at the 'aggrecanase' and the MMP sites. Characterization of MT1-MMP catabolic activities on the interglobular domain of aggrecan. , 1998, The Biochemical journal.

[35]  Y. Okada,et al.  Membrane Type 1 Matrix Metalloproteinase Digests Interstitial Collagens and Other Extracellular Matrix Macromolecules* , 1997, The Journal of Biological Chemistry.

[36]  L. Bourguignon,et al.  Overexpression of CD44 in pl85(neu)-transfected NIH3T3 cells promotes an up-regulation of hyaluronic acid-mediated membrane-cytoskeleton interaction and cell adhesion. , 1996, Oncogene.

[37]  D. Grignon,et al.  Membrane type 1-matrix metalloproteinase (MT1-MMP) and MMP-2 immunolocalization in human prostate: change in cellular localization associated with high-grade prostatic intraepithelial neoplasia. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[38]  Borland,et al.  Forms and functions of CD44 , 1998, Immunology.

[39]  K. Tanabe,et al.  Involvement of CD44 in matrix metalloproteinase‐2 regulation in human melanoma cells , 1999, International journal of cancer.

[40]  Y. Okada,et al.  Enhanced production and activation of progelatinase A mediated by membrane-type 1 matrix metalloproteinase in human oral squamous cell carcinomas: Implications for lymph node metastasis , 2004, Clinical & Experimental Metastasis.

[41]  J. R. de los Toyos,et al.  Lymphocyte recognition of high endothelium: antibodies to distinct epitopes of an 85-95-kD glycoprotein antigen differentially inhibit lymphocyte binding to lymph node, mucosal, or synovial endothelial cells , 1987, The Journal of cell biology.

[42]  W. Jiang,et al.  Inhibition of cancer cell motility and invasion by interleukin-12 , 1995, Clinical & Experimental Metastasis.

[43]  C. López-Otín,et al.  Cellular Mechanisms for Human Procollagenase-3 (MMP-13) Activation , 1996, The Journal of Biological Chemistry.

[44]  K. Mimori,et al.  Clinical significance of MT1-MMP mRNA expression in breast cancer. , 2001, Oncology reports.

[45]  D. Gotley,et al.  Expression of antisense CD44 variant 6 inhibits colorectal tumor metastasis and tumor growth in a wound environment. , 1998, Cancer research.

[46]  A. Perschl,et al.  Variant cell lines selected for alterations in the function of the hyaluronan receptor CD44 show differences in glycosylation , 1995, The Journal of experimental medicine.

[47]  W. Jiang,et al.  Quantification of tumour cell-endothelial cell attachment by 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine (DiI). , 1997, Cancer letters.

[48]  Z. Werb,et al.  New functions for the matrix metalloproteinases in cancer progression , 2002, Nature Reviews Cancer.

[49]  G. Giannelli,et al.  Role of Cell Surface Metalloprotease Mt1-Mmp in Epithelial Cell Migration over Laminin-5 , 2000, The Journal of cell biology.

[50]  J. Bell,et al.  Genomic structure of DNA encoding the lymphocyte homing receptor CD44 reveals at least 12 alternatively spliced exons. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[51]  I. Stamenkovic,et al.  Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. , 2000, Genes & development.

[52]  L. Milstone,et al.  Growth and differentiation regulate CD44 expression on human keratinocytes , 1999, In Vitro Cellular & Developmental Biology - Animal.

[53]  S. Arii,et al.  Membrane-type matrix metalloproteinase-1(MT1-MTP) gene is overexpressed in highly invasive hepatocellular carcinomas. , 1998, Journal of hepatology.

[54]  E. Bartnik,et al.  Assembly of pericellular matrices by COS-7 cells transfected with CD44 lymphocyte-homing receptor genes. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[55]  T. Yoshino,et al.  Binding of human leukocytes to fibronectin is augmented by an anti-CD44 mAb (TL-1) and blocked by another anti-CD44 mAb (Hermes-3) but not by anti-VLA-4/VLA-5 mAbs. , 1997, Immunobiology.

[56]  C. López-Otín,et al.  Induction of matrix metalloproteinase activation cascades based on membrane-type 1 matrix metalloproteinase: associated activation of gelatinase A, gelatinase B and collagenase 3. , 1998, The Biochemical journal.

[57]  L. Bourguignon,et al.  Involvement of CD44 and its variant isoforms in membrane-cytoskeleton interaction, cell adhesion and tumor metastasis , 1995, Journal of Neuro-Oncology.