Lysophosphatidic acid-depleted serum, hepatocyte growth factor and stem cell growth factor stimulate colony growth of small cell lung cancer cells through a calcium-independent pathway.
Serum stimulates both Ca2+ mobilization and colony growth of many small cell lung cancer (SCLC) cell lines, but the factors involved remain unknown. We demonstrate that 1-oleoyl-lysophosphatidic acid (LPA), like serum, induced a dose-dependent increase in intracellular Ca2+ in the H-510, H-345, and H-69 SCLC cell lines with half maximal concentrations of 18 nM, 22 nM, and 20 nM, respectively. Two lines of evidence revealed that LPA was the major factor in serum responsible for mobilizing Ca2+ in these SCLC cell lines: (a) both LPA and serum exhibited cross desensitization in the Ca2+ mobilization assay; and (b) phospholipase B pretreatment of either LPA or serum prevented the ability of these agents to stimulate Ca2+ mobilization. In marked contrast, LPA at concentrations between 2 nM and 20 microM, unlike serum, failed to stimulate colony formation. Furthermore, phospholipase B treatment of serum did not inhibit serum-induced colony formation. We therefore searched for growth factors which could induce colony growth through a Ca(2+)-independent pathway. We found that both human recombinant hepatocyte growth factor and stem cell growth factor increased colony growth, but failed to stimulate an increase in intracellular Ca2+ in the H-510, H-345, and H-69 SCLC cell lines. Our results indicate that LPA-depleted serum, hepatocyte growth factor, and stem cell growth factor stimulate colony formation in SCLC cells through a Ca(2+)-independent pathway.
Seckl
M J
MJ
Imperial Cancer Research Fund, London, United Kingdom.
Seufferlein
T
T
Rozengurt
E
E
D001790:Blood Physiological Phenomena; D002118:Calcium / Q000378:metabolism*; D018288:Carcinoma, Small Cell / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008245:Lysophospholipase / Q000494:pharmacology; D008246:Lysophospholipids / Q000502:physiology*; D019089:Stem Cell Factor; D014407:Tumor Cells, Cultured
D016298:Hematopoietic Cell Growth Factors; D008246:Lysophospholipids; D019089:Stem Cell Factor; D017228:Hepatocyte Growth Factor; D008245:Lysophospholipase; D002118:Calcium