Inflammatory breast carcinoma (IBC) is characterized by florid tumor emboli within lymphovascular spaces. Methods: Using a human-scid model of IBC. we have conceptually divided this phenotype into three parts. Results: 1) The tumor cell embolus (IBC spheroid) forms on the basis of an intact and overexpresscd E-cadherin / α, β- catenin axis which mediates tumor cell-tumor cell adhesion analogous to the embryonic blastocyst and accounts for both the compactness of the embolus and its complete dissolution with anti-E-cadherin antibodies. The compactness of the embolus results in its resistance to chemotherapy/radiation therapy and its efficiency at metastasis formation. 2) The tumor cell embolus (IBC spheroid), in contrast, fails to bind the surrounding vascular endothelial cells because of complete absence of sialyl-Lewis X/A carbohydrate ligand-binding epitopes on its overexpressed MUCI which are necessary for binding endothethial cell E-selectin. This tumor cell-endothethial cell aversion further contributes to the compactness of the IBC spheroid and its passivity in metastasis dissemination. 3) The tumor cell embolus finds itself within the vascular lumen in the first place because it stimulates a vascular channel to form around it rather than intravasating into a pre-existing lymphatic or capillary. The enveloping vascular channel does not form from angiogenesis but rather from vasculogenesis as evidenced by experiments where tumor cell emboli (IBC spheroids) are admixed with murine embryonal fibroblasts labeled with green fluorescent protein (GFP) and injected into scid mice. Tumor emboli are observed within lymphovascular spaces where the endothethial cells express vasculogenesis markers as well as endothethial markers: von Willebrand factor and vascular endothethial growth factor receptor (VEGF-R). These endothelial cells also express GFP, evidence that they must have formed from the injected GFP-labeled murine embryonal fibroblasts. Conclusion: The molecular basis of IBC then provides a mechanism by which IBC bypasses the traditional steps of intravasation, dissemination and extravasation in its metastatic pathway.
|Original language||English (US)|
|Number of pages||1|
|Journal||Breast Cancer Research and Treatment|
|State||Published - Dec 1 2001|
All Science Journal Classification (ASJC) codes
- Cancer Research