ObjectiveFibroblast activation protein (FAP) plays a vital role in tumor invasion and metastasis. Previous studies have reported its prognostic value in different tumors. However, the results of these reports remain controversial. In this study, a meta-analysis was performed to clarify this issue.MethodsA search of the PubMed, Embase and CNKI databases was conducted to analyze relevant articles. The outcomes included the relations between FAP expression and histological differentiation, tumor invasion, lymph node metastasis, distant metastasis and overall survival (OS). Sensitivity analysis by FAP expression in different cells and tumor types were further subjected to sensitivity analyses as subgroups. Pooled odds ratios (ORs) and hazard ratios (HRs) were evaluated using the random-effects model.ResultsThe global analysis included 15 studies concerning various solid tumors. For global analysis, FAP overexpression in tumor tissue displayed significant associations with poor OS and tumor progression (OS: HR = 2.18, P = 0.004; tumor invasion: OR = 4.48, P = 0.007; and lymph node metastasis: OR = 3.80, P = 0.004). The subgroup analyses yielded two notable results. First, the relation between FAP overexpression and poor OS and tumor lymph node metastasis was closer in the patients with FAP expression in tumor cells. Second, the pooled analyses of colorectal cancers or pancreatic cancers all indicated that FAP overexpression was associated with a detrimental OS (HR: 1.72, P = 0.009; HR: 3.18, P = 0.005, respectively). The magnitude of this effect was not statistically significant compared with that in patients with non-colorectal cancers or non-pancreatic cancers. These analyses did not display a statistically significant correlation between FAP expression and histological differentiation and distant metastasis in all of the groups.ConclusionsFAP expression is associated with worse prognosis in solid tumors, and this association is particularly pronounced if FAP overexpression is found in the tumor cells rather than the stroma.

The presence of IL-17-positive cells is observed in a variety of inflammatory associated cancers and IL-17 has been found to be involved in angiogenesis. However, it remains unclear how IL-17 might contribute to tumor angiogenesis. In our study, IL-17 enhanced the formation of vessel-like tubes in HUVECs both directly (when HUVECs were incubated with IL-17) and indirectly (when HUVECs were incubated in conditioned cell media (CCM) from IL-17-treated cancer cells). Our results from experiments using siRNA-mediated knockdowns of STAT3 and GIV suggest that the effects of IL-17 were mediated by activating STAT3/GIV signaling in NSCLC cells and subsequently up-regulating its downstream target VEGF. Consistent with these findings, immunostaining experiments on human NSCLC tissues indicated that IL-17 and GIV expression were significantly and positively associated with increased tumor vascularity. The clinical significance of IL-17 was authenticated by our finding that the combination of intratumoral IL-17 + cells and GIV expression served as a better prognosticator for survival than either marker alone. Therefore, our finding highlights a novel aspect of STAT3/GIV pathway in the IL-17 promotes tumor angiogenesis of NSCLC.

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CRS and HIPEC represent the standard treatment strategy for selected patients with MPM, and patients with unresectable tumors can benefit from the combined treatment of chemotherapy, radiotherapy, and immunotherapy.

A7R peptide (ATWLPPR), a ligand of the NRP-1 receptor, regulates the intracellular signal transduction related to tumor vascularization and tumor growth. Here, we designed A7R-cysteine peptide (A7RC) surface modified paclitaxel liposomes (A7RC-LIPs) to achieve targeting delivery and inhibition of tumor growth and angiogenesis simultaneously. The cytotoxicity, inhibiting angiogenesis, and internalization of various liposomes by cells were assessed in vitro to confirm the influence of the peptide modification. The accumulations of A7RC-LIPs in various xenografts in mice were tracked to further identify the function of the peptide on the liposomes' surface. The results confirmed that A7RC peptides could enhance the uptake of vesicles by MDA-MB-231 cells, leading to stronger cytotoxicity in vitro and higher accumulation of vesicles in MDA-MB-231 xenografts in vivo. In addition, A7RC peptides enhanced the inhibitory effects of LIPs on the HUVEC tubular formation on Matrigel. The A7RC-LIPs may be promising drug carriers for anticancer therapy.