Breast tumors metastasis

In human breast tumor cell lines, endothelins have been reported to induce CCR7 expression at both mRNA level and protein level through activation of endothelin receptor A (ET-RA) in a hypoxia-inducible factor-la (HIF-la)-dependent manner [40]. The endothelin system includes three small 21-amino acid peptides ligands (ET-1, ET-2, and ET-3), two G-protein-coupled receptors (ET-RA and ET-RB), and two activating peptidases [41]. Increased expression of endothelins and their receptors was found in invasive breast cancer compared to normal breast tissues or benign fibroadenomas [42, 43]. In human primary breast cancer, endothelin expression was correlated with CCR7 expression, both of which were associated with LN metastasis [40]. 

Skobe, M., T. Hawighorst, D. G. Jackson, R. Prevo, L. Janes, P. Velasco, L. Riccardi, K. Alitalo, K. Claffey, and M. Detmar. 2001. Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med 7 192-198. 

Sacco MG, Cato EM, Ceruti R, Soldati S, Indraccolo S, Caniatti M, Scanziani E, Vezzoni P. Systemic gene therapy with anti-angiogenic factors inhibits spontaneous breast tumor growth and metastasis in MMTVneu transgenic mice. Gene Ther 2001 8 67-70. 

Allan AL, Vantyghem SA, Tuck AB, Chambers AF. Tumor dormancy and cancer stem cells implications for the biology and treatment of breast cancer metastasis. Breast Dis 2006 26 87-98. 

Zhang ZH, Chen Y, Zhao HJ, Xie CY, Ding J, Hou YT. Silencing of heparanase by siRNA inhibits tumor metastasis and angiogenesis of human breast cancer in vitro and in vivo. Cancer Biol Ther 2007 6 587-595. 

The complexity of oncogenic process, involving somatic multiple mutations coupled with variability in the host s genetic constitution, produces a disease of enormous complexity. That is why Nevins et al. believe that 100 breast cancer patients may represent 100 distinct diseases [47]. The concept of each tumor as an individual was documented during the classification of breast carcinomas, because repeated samplings of the same tumor, either before and after chemotherapy or as a tumor-metastasis pair, were found to have much more similarity to each other than to any other tumor studied [49]. Furthermore, different foci in an individual may have distinct profiles and clonally related tumors in the same individual can show different expression patterns owing to divergent histories [50]. 

Cowin P, Rowlands TM, Hatsell SJ (2005) Cadherins and catenins in breast cancer. Curr Opin Cell Biol 17 499-508 Crnic I, Strittmatter K, Cavallaro U et al (2004) Loss of neural cell adhesion molecule induces tumor metastasis by up-regulating lymphangiogenesis. Cancer Res 64 8630-8638... 

---