Gene profile analysis of colorectal cancer cell lines by cDNA macroarray

Abstract

Abstract. In order to identify high-risk groups of patients with cancer, understanding the mechanisms of invasion and metastasis from the viewpoint of gene expression is required; in particular, the changes in gene expression as tumours gain the ability to metastasise. Using a rat model of metastatic colorectal cancer (CRC), we determined the expression profiles of CRC cells that metastasised to the liver and the lung. In the hepatopulmonary metastasis model, metastasising ability increased with successive transplanted cell line generations. No significant differences in cellular proliferation ability were seen between the original cell line and succeeding metastatic cell lines. Analysis using cDNA macroarray showed that metastasising ability was associated with increased expression of integrin ß4, γ-catenin, Smad 7, Bax, Bcl-2, c-fos and TGF-·, and a particularly marked increased expression of TGF-ß, PDGFb, Cdk4 and Rho B. Expression of both Rho GDIß and Gelsolin was reduced. These results suggest that high metastasising ability does not derive from a single gene, but rather through accumulated changes in the expression of several different genes.

Modification of the Primary Tumor Microenvironment by Transforming Growth Factor α-Epidermal Growth Factor Receptor Signaling Promotes Metastasis in an Orthotopic Colon Cancer Model

“…Supportive evidence for the involvement of TGF␣ in metastasis comes from a recent study that identified TGF␣ as a member of the gene set that that identifies colorectal cancer cells that metastasize to the liver. 64 Alternatively, it has been known for some time now that a high vascular density increases the likelihood that tumor cells will enter the systemic circulation and reach distal organs of metastasis, 65 and we found that C9 tumors are perfused by a greater number of blood vessels than tumors that secrete lesser amounts of TGF␣. Tumor blood vessels are considered to be inherently leaky, which makes them more susceptible to penetration by tumor cells, 26 but whether the slight increase in vascular density observed in C9 tumors (15 and 25% increase over KM12C and C10-TGF␣, respectively) is responsible for their enhanced ability to form liver metastases is difficult to determine.…”

The Role of Epidermal Growth Factor Receptor in Cancer Metastasis and Microenvironment

“…Supportive evidence for the involvement of TGF α in metastasis comes from a recent study that identified TGF α as a member of the gene set that that identifies colorectal cancer cells that metastasize to the liver [57]. Alternatively, it has been known for some time now that a high vascular density increases the likelihood that tumor cells will enter the systemic circulation and reach distal organs of metastasis [58], and we found that the activation of autocrine and paracrine TGF α /EGFR signaling networks affects the tumor microenvironment in colon cancer and determines its impact on the formation of metastases.…”

Functional blocking of specific integrins inhibit colonic cancer migration

“…These subunits have established key roles in colorectal cancer metastasis. Subunit b4 has been shown to be upregulated in colorectal liver and lung metastases [40]. All three subunits a6, a2 and b4 have been shown previously to be involved directly with cancer cell migration [12] and to associate with ADAM9-S, a protease which cleaves laminin and promotes cancer cell invasion [41].…”