The Epithelial Biochemistry Laboratory

Epithelial Biochemistry Laboratory

Role of laminin-10 in colon cancer metastasis

For many cancers, the spread of cancers to distant sites (metastasis) and subsequent growth kills cancer patients rather than the primary tumour. The ability to prevent the spread of tumour cells would assist current cancer treatments. This requires that factors that promote the spread of tumour cells are first identified and their behaviour analysed. In the case of colon tumour cells, we have shown that the growth factor EGF is involved the spreading of these cells. We have also identified another protein, laminin-10, which is secreted by colon cancer cells and which facilitates cell spreading and movement. Our current aim is to follow up these observations by developing specific peptides and antibodies against laminin-10 and then use them to detect and/or disrupt the behaviour of this protein. For example, the distribution of laminin-10 in normal colonic epithelium can be compared against that in primary and metastatic colonic neoplasms. Also, the effects of laminin-10 antagonists (alone or with inhibitors of other relevant signalling pathways) on colon tumour growth, proliferation and metastasis can be investigated. We are also generating large quantities of pure laminin-10 for these studies, most notably for the generation of anti-laminin-10 antibodies.

Bioassay of the action of purified laminin-10 on colon cell spreading.

Lab members involved in the research:

Publications:
Laminin-10 mediates basal and EGF-stimulated motility of human colon carcinoma cells via alpha(3)beta(1) and alpha(6)beta(4) integrins.
Pouliot N, Nice EC, Burgess AW.
Exp Cell Res. 2001 May 15;266(1):1-10. [Medline entry]

Colon cancer cells adhesion and spreading on autocrine laminin-10 is mediated by multiple integrin receptors and modulated by EGF receptor stimulation.
Pouliot N, Connolly LM, Moritz RL, Simpson RJ, Burgess AW.
Exp Cell Res. 2000 Dec 15;261(2):360-71. [Medline entry]

Multiple autocrine factors including an extracellular matrix protein are required for the proliferation and spreading of human colon carcinoma cells in vitro.
Pouliot N, Burgess AW.
Growth Factors. 2000;18(1):31-49. [Medline entry]