PTH-related protein enhances LoVo colon cancer cell proliferation, adhesion, and integrin expression.
Parathyroid hormone-related protein (PTHrP) has been localized in human colon cancer tissue and cell lines. Tumor cell adhesion to extracellular matrix (ECM) proteins plays a major role in the invasion and metastasis of tumor cells, and is mediated via integrin subunits. The LoVo human colon cancer cell line was used as a model system to study the effects of PTHrP on cell proliferation and adhesion to ECM proteins found in normal liver. Clones of LoVo cells engineered to overexpress PTHrP by stable transfection with a PTHrP cDNA showed enhanced cell proliferation vs. control (empty vector-transfected) cells. PTHrP-overexpressing cells also showed significantly higher adhesion to collagen type I, fibronectin, and laminin, and enhanced expression of the [symbol: see text] integrin subunits. These results indicate that PTHrP may play a role in colon cancer invasion and metastasis by increasing cell proliferation and adhesion to the ECM via upregulation of proinvasive integrin expression.
Shen
Xiaoli
X
Department of Pharmacology and Toxicology, University of Texas Medical Branch, 10th and Market Streets, Galveston, TX 77555, USA.
Falzon
Miriam
M
D000135:Acid Phosphatase / Q000378:metabolism; D015152:Blotting, Northern; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D000242:Cyclic AMP / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D005822:Genetic Vectors; D006801:Humans; D007118:Immunoassay; D039421:Integrin alpha2 / Q000378:metabolism; D039482:Integrin alpha5 / Q000378:metabolism; D039503:Integrin alpha6 / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D039663:Integrin beta4 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D009362:Neoplasm Metastasis; D044162:Parathyroid Hormone-Related Protein / Q000502:physiology*; D010957:Plasmids / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
D018076:DNA, Complementary; D005353:Fibronectins; D039421:Integrin alpha2; D039482:Integrin alpha5; D039503:Integrin alpha6; D019012:Integrin beta1; D039663:Integrin beta4; D016023:Integrins; D007797:Laminin; D044162:Parathyroid Hormone-Related Protein; D000242:Cyclic AMP; D000135:Acid Phosphatase