P-selectin mediated attachment of small cell lung carcinoma to
endothelial cells.
Pottratz, Scott T., Trevina D. Hall, William M. Scribner, H. N.
Jayaram, and V. Natarajan.
Division of Pulmonary and Critical Care Medicine, Laboratory for
Experimental Oncology, Indiana University School of Medicine,
Indianapolis, Indiana 46202
APStracts 3:0138L, 1996.
Small cell lung carcinoma (SCLC) frequently metastasizes early in the
course of the disease. P-selectin (P-sel), a cell adhesion molecule
expressed on activated platelets and endothelial cells (EC), has
previously been demonstrated to mediate binding of platelets to SCLC.
We hypothesized that P-sel facilitates attachment of SCLC to EC,
acting as an important factor in SCLC metastasis. To test this
hypothesis, attachment of H82 cells (SCLC cell line) to EC was
quantified. Attachment of H82 cells to 12-O-tetradecanoyl phorbol-13
-acetate (TPA)-activated EC was increased compared to control EC.
Increased attachment of H82 cells to EC was apparent after 10 minutes
of TPA activation, reached a peak after 30 minutes and returned to
baseline after 120 minutes of exposure. The TPA-induced increase in
H82 cell attachment to EC was inhibited by addition of anti-P-sel
antibodies but not by addition of anti-E-selectin antibodies. The
TPA-induced increase in H82 cell attachment was likely mediated by
activation of EC protein kinase C (PKC). Pretreatment of the EC with
PKC inhibitors effectively blocked the TPA-mediated increase in H82
cell attachment. In addition, prolonged exposure of EC to TPA
resulted in decreased expression of the PKC- and PKC- isoforms. These
data indicate for the first time that attachment of SCLC to activated
EC appears to be mediated by increased expression of P-sel on the EC
surface which may result from activation of specific isoforms of PKC.
Received 11 December 1995; accepted in final form 24 July 1996.
APS Manuscript Number L359-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 August 1996