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Heterogeneity of the motility responses in malignant tumor cells: A biological basis for the diversity and homing of metastatic cells
Author(s) -
Kohn Elise C.,
Francis Elizabeth A.,
Liotta Lance A.,
Schiffmann Elliott
Publication year - 1990
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/ijc.2910460225
Subject(s) - homing (biology) , motility , biology , cancer research , pathology , medicine , microbiology and biotechnology , ecology
Tumor metastasis requires highly motile cells that can respond to appropriate stimuli. A2058 human melanoma cells were shown previously to secrete a highly potent autocrine motility factor (AMF) that stimulates chemokinetic movement. We have shown that the insulin polypeptides (IPS; insulin‐like growth factors I and II [IGF‐I, ‐II] and insulin) stimulated A2058 cell chemotaxis and chemokinesis. We now report that the IPs and AMF stimulate locomotion in other human malignant cell lines. Insulin (100 nm) induced motility of up to 50% of the magnitude of the AMF response in human carcinoma lines MDA‐231 (breast), T24 (bladder), and OVCAR3 (ovarian). The tumorigenic and metastatic SR Ha‐ ras ‐transfected rat embryo fibroblast cell line responded to insulin with both chemotaxis and chemokinesis and was 100% of that seen for AMF. The ED 50 for IGF‐I in the carcinoma cell lines was in the order of I nm, but the magnitude of the responses at this concentration was 40% of the AMF‐stimulated response, with the exception of the A2058 cells, which were maximally stimulated at I nn. IGF‐II induced maximal motility of 75 to 130% of the AMF‐stimulated response in the carcinoma lines with ED 50 , of <10 nM. IGF‐II‐stimulated motility in the carcinoma lines was predominantly chemotactic by modified checkerboard analysis. Cell pretreatment with pertussis toxin inhibited 90‐100% of AMF‐induced motility, whereas migration to the IPS was not pertussis toxinsusceptible. In growth studies, IGF‐I induced mitogenesis up to 140% of basal media control growth. In general, maximal growth stimulation was seen at 100 nn IGF‐I, and optimal migration was seen at 10 nM IGF‐I. The IGFs are secreted by normal stroma in a number of organs that are common sites for primary and metastatic disease. Therefore, we suggest that IPS may be important homing and mitogenic signals for tumor cells in the process of invasion and metastasis and that the differential motility stimulation and respective mechanisms of action by these physiologically important agents may underlie the diversity of the metastatic process.