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Liver endothelial E‐selectin mediates carcinoma cell adhesion and promotes liver metastasis
Author(s) -
Brodt Pnina,
Fallavollita Lucia,
Bresalier Robert S.,
Meterissian Sarkis,
Norton Christine R.,
Wolitzky Barry A.
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19970516)71:4<612::aid-ijc17>3.0.co;2-d
Subject(s) - metastasis , extravasation , cancer research , endothelium , endothelial stem cell , cell adhesion , cytokine , leukocyte extravasation , cell–cell interaction , selectin , cell adhesion molecule , cell culture , biology , pathology , medicine , immunology , cell , cancer , endocrinology , in vitro , biochemistry , genetics
E‐selectin is a cytokine‐inducible endothelial cell adhesion receptor which is involved in the process of leukocyte rolling, the first in a cascade of interactions leading to leukocyte transmigration. Several studies have implicated this receptor in carcinoma cell adhesion to the endothelium, an interaction thought to be required for tumor extravasation during metastasis. To study the role of this receptor in the process of metastasis, we utilized a murine carcinoma line H‐59 which is highly metastatic to the liver in vivo . When adhesion of H‐59 cells to primary cultures of murine hepatic endothelial cells was measured, it was found that the tumor cells had a low which basall of adhesion to the sinusoidal endothelial cells, which could be significantly and specifically augmented by pre‐activation of the endothelial cells with rTNFα. This incremental increase in adhesion to the activated endothelium could be completely and specifically abolished by a neutralizing monoclonal antibody to murine E‐selectin (MAb 9A9). Similar results were obtained with 2 highly metastatic human colorectal carcinoma lines, HM 7 and CX‐1, but not with a second murine subline, M‐27, which is poorly metastatic to the liver. To assess the role of E‐selectin in metastasis to the liver in vivo , the effect of MAb 9A9 on experimental liver metastasis was evaluated using the syngeneic H‐59 model. We show here that this antibody caused a marked, specific and Fc‐independent inhibition of experimental liver metastasis, reducing the median number of metastases by 97% relative to the control groups. Our results provide evidence that endothelial E‐selectin is a mediator of carcinoma metastasis to the liver. Int. J. Cancer 71:612‐619, 1997. © 1997 Wiley‐Liss, Inc.