Endothelin-2 Differential Expression in Normal and Early-Stages of Colon Cancer Development

Abstract

The endothelin family has been related with several pathological diseases including cardiovascular disorders, hypertension and cancer. However, little is known about endothelin system in early stages of colorectal cancer and there are no studies evaluating differences in proximal and distal colon segments. To deepen in this issue, we have studied the endothelin's family gene and protein expression in normal mice and early stage of a mice model of Azoxymethane (AOM) and Dextran Sodium Sulphate (DSS) induced colorectal cancer in proximal and distal segments. Additionally, using nonlinear microscopy (NLM) techniques, we have characterized collagen changes in early stages of cancer disease development. In the present study, we have found significant differential gene expression and protein localization between these colon regions, which allow us to hypothesize a new role for the ET-2 as an early marker of colon cancer development.

Aspects of the endothelin system in colorectal cancer

“…In fact, in 80% of primary human colon cancers there is EDN-1 overexpression (33). In normal mucosa and early stage colon cancer cells there is still normal expression of EDN-1, but overexpression develops during later stages of colon cancer (15). The role of EDN-1 in cancer may be due to over-expression of EDN-1 or overexpression of its receptors, or their signaling pathways.…”

“…In comparison to EDN-1, which is distributed in all rat organs examined (13), EDN-2 expression is more restricted to certain human and rat organs, including the intestines (14). Interestingly, EDN-2 has an unequal distribution in the colon; it is immunolocalized at the middle and upper parts of a crypt in the proximal colon and in the base of crypts in the distal colon (15). Endothelin-2 is known as a hypoxia inducible and antihypoxic factor.…”