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Phorbol ester‐induced promyelocytic leukemia cell adhesion to marrow stromal cells involves fibronectin specific α5β1 integrin receptors
Author(s) -
MartinThouvenin V.,
Gendron M. C.,
Hogervorst F.,
Figdor C. G.,
Lanotte M.
Publication year - 1992
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041530113
Subject(s) - stromal cell , fibronectin , microbiology and biotechnology , integrin , cell adhesion , receptor , chemistry , biology , cancer research , extracellular matrix , cell , biochemistry
The human promyelocytic cell line NB4 exhibited a weak adhesion capacity in bone marrow‐derived stromal cells and their extracellular matrices (5–15% of adherent cells). Adhesion was enhanced by pulse‐treatment of cells with phorbolester (PMA 10 −7 M). Adhesion was induced within minutes, was fibronectin‐specific, and affected up to 100% of the treated cells. This biological response to PMA resulted from the activation of protein kinase C (PKC), since PKC inhibitors (staurosporine, sphingosine, CGP 41251, and calphostin C) prevented the phenomenon. Phenotypical analysis of integrin receptor expression (particularly FN receptors VLA‐4 and VLA‐5) at the membrane of untreated or PMA‐treated cells revealed that PMA induced no significant modification of the level of expression of these receptors. However, inhibition studies carried out with anti‐VLA monoclonal antibodies demonstrated that the FN‐specific adhesion triggered by PKC involved the α5β1 FN‐specific receptors (VLA‐5) We showed that the bindings of NB4 cells to fibronectin was RGD‐dependent. PMA‐induced adhesion was not correlated to phosphorylation of the VLA‐5 receptor. These findings may partially explain the malignant behaviour of these cells: The loss of their capacity to adhere to stomal cells may arrest differentiation and explain the large number of leukemic cells in the circulation. © 1992 Wiley‐Liss, Inc.