L’éternel et l’éphémère

GM-CSF promotes a supportive adipose and lung microenvironment in metastatic breast cancer

“…These findings were collected in vitro and in xenograft models, using different triple negative breast cancer lines and primary adipose progenitors. In parallel with other studies, which also reported an increased expression of the two molecules in the context of breast cancer [4, 5], we also described that the higher release was due to transcription up-regulation occurring in WAT- derived progenitors, when exposed to tumor cells [3]. Both ASCs and EPCs produced higher levels of GM-CSF and MMP9 in presence of breast cancer, further supporting the cooperation in tumor malignancy [3].…”

“…We recently demonstrated the existence of a regulatory axis between breast cancer cells and WAT- derived progenitors [3]. Granulocyte macrophage colony- stimulating factor (GM-CSF) was suggested as the tumor-released factor, which induced the expression of GM-CSF itself and metallopeptidase 9 (MMP9) in adipose progenitors.…”

“…The ablation of GM-CSF in tumor cells, achieved through siRNA delivery, prevented GM-CSF and MMP9 up-regulation in WAT-derived progenitors [3]. This suggested that GM-CSF may be required to alter WAT progenitors expression and to shift the adipose stroma to a supportive tumor microenvironment [3].…”

“…This suggested that GM-CSF may be required to alter WAT progenitors expression and to shift the adipose stroma to a supportive tumor microenvironment [3]. GM-CSF knock- down in xenografts or its neutralization in syngeneic diet-induced obese models was associated to a significant reduction of primary tumor growth, lung metastasis, and neoplastic angiogenesis and an increase in the number of immunosuppressive cells [3]. This is in contrast to some papers reporting an anti-tumor effect of GM-CSF in the context of breast cancer [6].…”

“…The increase of GM- CSF release in response to breast cancer progression was significant in obese mice, but not in lean mice, and more evident at the later stages of tumor progression [7]. Higher levels of plasma GM-CSF were also detected in our xenograft models based upon co-injection breast cancer cells and WAT progenitors, compared to mice injected with tumor cells alone [3]. These data support the role of adipose progenitors as the primary source of GM-CSF released into circulation.…”