A special linker between macrophage and hematopoietic malignant cells: membrane form of macrophage colony-stimulating factor.
The membrane form of macrophage colony-stimulating factor (mM-CSF) is an alternative splicing variant of this cytokine. Although its high expression was detected in hematopoietic malignancies, its physiologic and pathologic roles in hematopoietic system have not been established. In this report, stable transfectant clones expressing mM-CSF (Namalwa-M and Ramos-M) were obtained, which showed reduced proliferation potential in vitro. Moreover, the in vivo study showed that Namalwa-M and Ramos-M exhibited enhanced oncogenicity in tumor size in nude mice model, which could be inhibited by M-CSF monoclonal antibody. A remarkable increase in infiltrating macrophage and the vessel densities was found in tumor tissues formed by lymphoma cell lines that stably expressed mM-CSF, which suggested the involvement of macrophages in this process. The in vitro results using coculture system showed that macrophages could promote Namalwa-M and Ramos-M proliferation and activate extracellular signal-regulated kinase/mitogen-activated protein kinase signal pathway. In addition, the expression of murine origin vascular endothelial growth factor, basic fibroblast growth factor, and hepatocyte growth factor was elevated in Namalwa-M formed tumor tissues. These results suggested that mM-CSF should be a positive regulator in the development of hematopoietic malignancies by abnormally activating infiltrating macrophages, which in turn promote the malignant development. Thus, mM-CSF may be a critical linker between macrophages and malignant cells in the development of hematopoietic malignancies.
Wang
Lin
L
State Key Laboratory for Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Zheng
Guo-Guang
GG
Ma
Cui-Hua
CH
Lin
Yong-Min
YM
Zhang
Hai-Yan
HY
Ma
Yuan-Yuan
YY
Chong
Jing-Hui
JH
Wu
Ke-Fu
KF
D000818:Animals; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D005260:Female; D006413:Hematopoietic System / Q000166:cytology* / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor; D016173:Macrophage Colony-Stimulating Factor