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The alphaVbeta6 integrin regulates its own expression with cell crowding: implications for tumour progression
1Discipline of Surgical Science, Faculty of Medicine and Health Sciences, University of Newcastle, New South Wales, Australia.
International Journal of Cancer
|April 3, 2001
Summary
Colon cancer cells with integrin alphavbeta6 show increased growth and gelatinase B secretion at high densities. This integrin promotes its own expression via a protein kinase C pathway, sustaining tumor cell proliferation.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Integrin alphavbeta6 is implicated in tumor growth and invasion.
- High cell density can alter cellular behavior and signaling pathways in cancer.
Purpose of the Study:
- To investigate the role of integrin alphavbeta6 in colon cancer cell proliferation and matrix degradation.
- To elucidate the signaling mechanisms, particularly protein kinase C (PKC), involved in alphavbeta6 regulation at high cell densities.
Main Methods:
- Assessing alphavbeta6 expression in colon cancer cells at varying cell densities.
- Measuring gelatinase B secretion and activation.
- Investigating the involvement of protein kinase C (PKC) signaling pathways.
- Utilizing collagen matrix for in vitro tumor cell growth studies.
Main Results:
- High cell density selectively enhances alphavbeta6 expression in a PKC-dependent manner.
- Increased alphavbeta6 expression leads to marked gelatinase B secretion and activation.
- PKC activity significantly rises with cell confluence, especially in alphavbeta6-expressing cells.
- Inhibition of gelatinase B abolishes alphavbeta6-mediated tumor cell growth in collagen.
Conclusions:
- Integrin alphavbeta6 expression is upregulated by high cell density through a PKC-dependent pathway.
- A self-perpetuating cycle exists where alphavbeta6 sustains colon cancer progression by regulating its own expression and promoting matrix degradation.
- This mechanism facilitates tumor cell proliferation by overcoming crowding and restoring growth.
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