Collagen I but not Matrigel matrices provide an MMP-dependent barrier to ovarian cancer cell penetration
| Autor: | Theodore J. Brown, Maurice J. Ringuette, Katharine L. Sodek |
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| Rok vydání: | 2008 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty Stromal cell lcsh:RC254-282 03 medical and health sciences 0302 clinical medicine Cell Movement Laminin Cell Line Tumor Genetics medicine Animals Humans Neoplasm Invasiveness 030304 developmental biology Ovarian Neoplasms Basement membrane Wound Healing 0303 health sciences Matrigel Microscopy Confocal biology Cancer lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Matrix Metalloproteinases Pepsin A Rats Drug Combinations medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer cell biology.protein Cancer research Female Proteoglycans Collagen Peptides Ovarian cancer Wound healing Research Article |
| Zdroj: | BMC Cancer BMC Cancer, Vol 8, Iss 1, p 223 (2008) |
| ISSN: | 1471-2407 |
| DOI: | 10.1186/1471-2407-8-223 |
| Popis: | BackgroundThe invasive potential of cancer cells is usually assessedin vitrousing Matrigel as a surrogate basement membrane. Yet cancer cell interaction with collagen I matrices is critical, particularly for the peritoneal metastatic route undertaken by several cancer types including ovarian. Matrix metalloprotease (MMP) activity is important to enable cells to overcome the barrier constraints imposed by basement membranes and stromal matricesin vivo. Our objective was to compare matrices reconstituted from collagen I and Matrigel as representative barriers for ovarian cancer cell invasion.MethodsThe requirement of MMP activity for ovarian cancer cell penetration of Matrigel and collagen matrices was assessed in 2D transwell and 3D spheroid culture systems.ResultsThe broad range MMP inhibitor GM6001 completely prevented cell perforation of polymerised collagen I-coated transwell membranes. In contrast, GM6001 decreased ES-2 cell penetration of Matrigel by only ~30% and had no effect on HEY cell Matrigel penetration. In 3D culture, ovarian cancer cells grown as spheroids also migrated into surrounding Matrigel matrices despite MMP blockade. In contrast, MMP activity was required for invasion into 3D matrices of collagen I reconstituted from acid-soluble rat-tail collagen I, but not from pepsin-extracted collagen I (Vitrogen/Purecol), which lacks telopeptide regions.ConclusionMatrigel does not form representative barriers to ovarian cancer cells in either 2D or 3D culture systems. Our findings support the use of collagen I rather than Matrigel as a matrix barrier for invasion studies to better approximate critical interactions and events associated with peritoneal metastasis. |
| Databáze: | OpenAIRE |
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