Endoglin can suppress prostate cancer metastasis (at least in mice)
Posted Nov 24 2010 12:00am
Endoglin is a protein found in certain cell membranes. (Strictly speaking it is a type I membrane glycoprotein found on cell surfaces and is part of the TGFβ receptor complex). It has previously been shown that endoglin can suppress human prostate cancer cell invasion.
A new set of studies just reported by Lakshman et al. set out to investigate whether endoglin was able to have regulatory impact on metastatic behavior, on the growth of prostate cancer tumors, and/or on signaling pathways that are known to be linked to these two processes. The studies were carried out in a mouse model of human prostate cancer metastasis, so we should be very careful not to over-interpret any data from these studies. As we have said before, what works in mice has a strong tendency to not be repeatable in man, but still …
In their new study, Lakshman et al. were able to show that:
Progressive loss of endoglin activity was associated with progressive increases in the number of circulating prostate cancer cells and in the formation of soft tissue metastases.
Increased tumor growth and increased expression of Ki67 in tissue was seen only with complete endoglin loss.
The authors propose that because endoglin increased TGFβ-mediated suppression of cell growth in vitro and TGFβ-mediated signaling in tumor tissue, loss of this growth-suppressive pathway seems to play some role in the increased size of endoglin-deficient tumors. They conclude that endoglin is able to:
Suppress prostate cancer cell movement out of primary tumor
Suppress the formation of distant prostate cancer metastasis
Co-regulate tumor growth and metastatic behavior in human prostate cancer
It is relevant that small molecule therapeutic agents that are known to activate endoglin signaling are already being tested in man (and in woman).
There will need to be a great deal more evidence to support this hypothesis before the potential of endoglin signaling activation could be considered as an effective way to prevent the growth and metastasis of prostate cancer. However, with that reservation, it is of considerable scientific interest that we can now identify specific regulatory proteins that may be able to control such cancer growth and metastasis.