A novel human xenograft model of inflammatory breast cancer

The step of intravasation or lymphovascular invasion can be a rate-limiting step in the metastatic process. Inflammatory breast carcinoma manifests an exaggerated degree of lymphovascular invasion in situ; hence, a study of i ts molecular basis might shed Light on the general mechanism of lymphovascu lar invasion exhibited by all metastasizing cancers. To this end, we have e stablished the first human transplantable inflammatory breast carcinoma xen ograft ((MARY-X) in scid/nude mice. Whereas all other human xenografts grew as isolated s.c, nodules, MARY-X grew exclusively within murine lymphatics and blood vessels, and these latter elements and their supporting stroma c omprised, by murine Cot-l DNA analysis, 30% of the tumor. MARY-X, like its human counterpart, exhibited striking erythema of the overlying skin. MARY- X was estrogen receptor, progesterone receptor, Her-2/neu negative and p53, epidermal growth factor receptor positive, The primary tumor of origin of MARY-X exhibited identical markers, except that about 50% of its cells exhi bited Her-2/neu amplification. Comparative studies of MARY-X with noninflam matory xenografts indicated 10-20-fold overexpression of E-cadherin and MUC 1, findings that were reflected in actual cases of human inflammatory breas t cancer. MARY-X should allow us to further dissect out both the upstream r egulatory machinery and the downstream effector molecules responsible for t he inflammatory carcinoma phenotype.