(86e) Divergent Roles of CD44 and Carcinoembryonic Antigen in Colon Carcinoma Metastasis | AIChE

(86e) Divergent Roles of CD44 and Carcinoembryonic Antigen in Colon Carcinoma Metastasis


Dallas, M. - Presenter, Johns Hopkins University
Liu, G. - Presenter, Johns Hopkins Medical Institutions
Thomas, S. N. - Presenter, École Polytechnique Fédérale de Lausanne
Huso, D. L. - Presenter, Johns Hopkins Medical Institutions
Konstantopoulos, K. - Presenter, Johns Hopkins University

Cancer metastasis is a highly coordinated process in which cancerous cells separate from a primary tumor and enter the circulatory system, where they interact extensively with host cells before lodging in the target organ and forming metastatic colonies. Accumulating evidence suggests that E-, P-, and L-selectins facilitate metastasis by mediating specific interactions between selectin-expressing host cells and selectin ligands presented by tumor cells. Previous work in our lab identified and characterized the selectin ligands CD44v and carcinoembryonic antigen (CEA), both of which are glycoproteins irregularly expressed by tumorous cells. Mediated by siRNA, the stable, specific knockdown of these molecules led to a significant reduction in interactions between colon carcinoma cells and immobilized selectins. In this work, aimed at assaying the metastatic potential of these knockdown cells, we established a metastatic model in which LS174T colon carcinoma cells knocked-down for CD44, CEA, or CD44 and CEA were injected via the tail vein into NOG mice. Employing quantitative PCR as a highly quantitative, highly sensitive measure of tumor burden, we demonstrate that knockdown of CD44 significantly increased the ability of LS174T cells to lodge and grow in vital organ systems without affecting the systemic tumor burden. Conversely, we show that knockdown of CEA results in a dramatic, systemic decrease in metastatic potential. These findings provide evidence that CEA, but not CD44, may be a viable target molecule for therapeutics aimed at curbing colon carcinoma metastasis.