Stem cell factor is not essential for cell survival and proliferation of soft tissue sarcoma of neuroectodermal origin.
OBJECTIVE
Stem cell factor (SCF), and its receptor (c-kit) play key roles in the expansion and differentiation of hematopoietic progenitor cells, in melanoblasts and primordial germ cells, making it possible that SCF and c-kit are involved in neoplastic processes deriving from these cells. C-kit has been described to be expressed at different levels in neuroblastoma and in soft tissue sarcoma of neuroectodermal origin, and seems to be required for survival processes. In this study we investigate how c-kit expression is regulated and whether a SCF autocrine loop is essential for survival of sarcoma cell lines.


METHODS
C-kit modulation and internalization was evaluated incubating cells with rhSCF. Cell differentiation and proliferation experiments were performed to test whether c-kit expression is related to cell cycle progression or to differentiation processes. Cell cultures were treated with neutralizing antibody and antisense oligonucleotides in order to assess the possible significance of the SCF autocrine loop.


RESULTS
In vitro SCF stimulation induces c-kit down-regulation; this phenomenon could be connected with receptor internalization, and new protein synthesis is necessary for its re-expression. The cell proliferation arrest in G0/G1 does not modify c-kit expression while down-regulation of c-kit was demonstrated after cells had been treated with differentiating agents. SCF neutralization does not influence either the S phase or apoptosis in sarcoma cell lines.


CONCLUSIONS
In sarcoma cell lines, c-kit is regulated by differentiation processes; moreover our results suggest that c-kit activity, but probably not the SCF autocrine loop, is essential for survival of these cell lines.
Ricotti
E
E
Department of Pediatrics, University of Turin, Italy.
Bertorello
N
N
Vai
S
S
Pagani
A
A
Cordero Di Montezemolo
L
L
Madon
E
E
Basso
G
G
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D019898:Autocrine Communication; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D017599:Neuroectodermal Tumors / Q000378:metabolism* / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis / Q000187:drug effects* / Q000235:genetics; D012333:RNA, Messenger; D016196:S Phase / Q000187:drug effects / Q000276:immunology; D012509:Sarcoma / Q000378:metabolism* / Q000473:pathology; D019089:Stem Cell Factor / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D019089:Stem Cell Factor; D003994:Bucladesine; D003513:Cycloheximide; D019009:Proto-Oncogene Proteins c-kit