Protein‐kinase‐C inhibitor calphostin C reduces B16 amelanotic melanoma cell adhesion to endothelium and lung colonization

Bin Liu, Colette Renaud, Kevin K. Nelson, Yong Q. Chen, Rajesh Bazaz, Julie Kowynia, Jozsef Timar, Clement A. Diglio, Kenneth V. Honn

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

We recently reported that the Ca2+‐and phospholipids‐dependent protein kinase, protein kinase C (PKC), was involved in rat Walker carcinosarcoma cell adhesion to large‐vessel endothelium. We extended our studies to explore the role of this kinase in the adhesion to small‐vessel endothelium and lung colonization of murine B16 amelanotic melanoma (B16a). Sub‐populations of B16a cells, which differ in lung‐colonization potentials, were isolated by centrifugal elutriation from solid tumors. In this study, we demonstrate that cells from a high metastatic sub‐population (HM340), when compared with cells from a low metastatic sub‐population (LM180), exhibit elevated levels of total cellular as well as membrane‐bound PKC. The increase in PKC in cells from the HM340 correlates positively to their increased ability to adhere to murine pulmonary‐microvessel endothelial‐cell monolayer, and to form pulmonary colonies in syngeneic mice. Calphostin C, a potent and selective PKC inhibitor, decreases in a dose‐dependent manner the adhesion to endothelium and the lung colonization of cells from both the low and the high metastatic sub‐populations with IC50 at sub‐micromolar concentrations. In conclusion, our results suggest that PKC may be a key element in regulating tumor‐cell metastasis and that PKC inhibitors may be anti‐metastatic agents. © 1992 Wiley‐Liss, Inc.

Original languageEnglish
Pages (from-to)147-152
Number of pages6
JournalInternational Journal of Cancer
Volume52
Issue number1
DOIs
Publication statusPublished - Aug 19 1992

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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