Abstract
BackgroundChemokines play multiple roles in the development and progression in a variety of tumors. Chemokine (C-X-C motif) ligand 7 (CXCL7) has been found associated with pro-inflammatory responses, but its role in cancer growth remains unclear. Our previous study showed that R phase tumor infiltrating lymphocytes (TILs) produced large amounts of interleukin (IL)-6 which antagonized transforming growth factor (TGF)-β derived from CTVT to diminish the immune-suppressive microenvironment. Now we intend to determine the expression pattern of CXCL7 and the role of IL-6/TGF-β in CXCL7 induction during spontaneous progressive (P) and regressive (R) phases in canine transmissible venereal tumor (CTVT).ResultsWe have demonstrated that CXCL7 expressed at high level in P phase and down-regulated in R phase by western blot and real-time PCR. This suggested that CXCL7 expression was negatively correlated with the tumor growth. Co-culturing TILs with CTVT cells was found to reduce CXCL7 expression, while adding IL-6 blocking antibody reversed it. Moreover, in P phase CTVT, while IL-1β and TGF-β had no obvious effect on CXCL7 expression, IL-6 was found significantly to reduce CXCL7 expression in a dose-dependent manner. The mRNA expression results of CXCL7 receptor, CXCR2, further confirmed the effects of IL-6 concentration on the CXCL7 expression.ConclusionCXCL7 overexpression might be associated with the progressive growth of CTVT. The results shown here also suggest the role of CXCL7 in cancer development and the potential as the anti-cancer therapeutic target.
Highlights
Chemokines play multiple roles in the development and progression in a variety of tumors
The immune systems of most hosts eventually reject the transplanted cells in the regression (R) phase [5]. One mechanism for this rejection is related to interleukin (IL)-6 produced by tumor-infiltrating lymphocytes (TIL) that counteract the activities of transforming growth factor (TGF)-β [4]
Western blotting revealed that in comparison with the R phase, the CXCL7 protein was significantly upregulated in the canine transmissible venereal tumor (CTVT) P phase (Figure 1B)
Summary
Chemokines play multiple roles in the development and progression in a variety of tumors. The tumor cells effectively evade the host’s histocompatibility (MHC) barrier for long periods, and transplanted cells grow liberally in the progression (P) phase for a few months or over 1 year [2,3] This immunoevasion was found partly because of the high concentration of tumor-secreted Transforming growth factor-β (TGF-β), which inhibits tumoral MHC antigen expression and the activity of natural killer cells [4]. The immune systems of most hosts eventually reject the transplanted cells in the regression (R) phase [5] One mechanism for this rejection is related to interleukin (IL)-6 produced by tumor-infiltrating lymphocytes (TIL) that counteract the activities of TGF-β [4]. CTVT is one of the few tumors that allow us to study detailed dynamic changes in host–cancer interactions during spontaneous regression of a tumor
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