Premium
Granulocyte‐macrophage colony‐stimulating factor induces human melanoma‐cell migration
Author(s) -
Kohn Elise C.,
Hollister Gambrill H.,
Liotta Lance A.,
Schiffmann Elliott,
Kohn Elise C.,
Wahl Sharon,
Dipersio John D.
Publication year - 1993
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.2910530618
Subject(s) - chemotaxis , biology , cancer research , melanoma , autocrine signalling , cell migration , colony stimulating factor , granulocyte macrophage colony stimulating factor , cell culture , receptor , immunology , cell , microbiology and biotechnology , cytokine , stem cell , haematopoiesis , biochemistry , genetics
Tumor metastasis is the primary cause of death for cancer patients. The metastatic cascade requires successful tumor cell invasion into and through vascular and parenchymal barriers. We have shown that autocrine motility factor (AMF, autotaxin) and the insulin‐like growth factors (IGFs) induce tumor‐cell migration. Since granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) has been shown to prime neutrophils for chemotaxis, we have therefore studied the influence of GM‐CSF upon tumor cells and report that GM‐CSF stimulates migration of these cells in a dose‐dependent fashion. The ED 50 for A2058 human melanoma cell line chemotaxis to GM‐CSF is approx. 60 pM. The motile response to GM‐CSF was additive to that of IGF‐1 and AMF, both of which are potent attractants for tumor cells. Pre‐treatment of cells for 2 hr with non‐toxic concentrations of pertussis toxin (PT) or amiloride resulted in a 50% inhibition of chemotaxis to GM‐CSF. Therefore, GM‐CSF, through PT‐ and amiloride‐sensitive signal pathways, is a potent attractant for melanoma cells, the response to which is additive to that of other attractants. The presence of the GM‐CSF receptor in A2058 melanoma cells was indicated by Northernblot analysis which identified message transcripts of 2.1 and 3.0 kb. These data emphasize the versatility of the melanoma cell migration response to an array of cytokines, including GM‐CSF.