Abstract
Tumor angiogenesis is known to be regulated by growth factors secreted by host and tumor cells. Despite the importance of tumor vasculature and angiogenic heterogeneity in solid tumors, few studies have compared the vasculature in different regions of human cancer. Blood vessels from different regions of carcinomas might have morphofunctional implications in tumor angiogenesis. In the present study, therefore, we have examined the relationship between microvascular density (MVD) and vascular endothelial growth factor (VEGF) expression and alpha smooth muscle actin (α-SMA) expression in the center of the tumor (CT), periphery (P) and metastasis (M) regions from gastrointestinal carcinomas (GITC), as well as the association of MVD with clinicopathological factors. Surgically resected specimens corresponding to the CT, P and M from 27 patients were examined for FVIII, VEGF and α-SMA by immunohistochemistry. The MVD was not significantly different in the CT, P and M regions from GITC. The MVD in the VEGF positive group was significantly higher than in the VEGF negative group (CT, p = 0.034; P, p = 0.030; M, p = 0.032). The MVD as a function of α-SMA expression was also significantly higher in the CT and P region compared to the M region (p = 0.0008). In conclusion, the MVD association with VEGF and α-SMA expression, might indicate an increase of the number of neoformed and preexisting blood vessels uniformly or partially covered by pericytes in different regions of GITC, suggesting that not only MVD and VEGF are important parameters to the tumor vasculature, but also blood vessels maturation is a crucial factor for gastrointestinal tumor angiogenesis regulation and possible target of vascular therapy.
Highlights
The importance of tumor angiogenesis in the growth, progression and metastasis of solid tumors is widely known
The proportion of blood vessels covered by pericytes D-SMA+ uniformly distributed was higher in the P region (82.36%) compared to the center of the tumor (CT) (45.46%) and M region (59.10%). These results indicate that the tumor vasculature of gastrointestinal carcinomas (GITC) is composed by a high proportion of blood vessels covered uniformly by pericytes D-SMA+ predominantly in the P region, as well as blood vessels with pericytes
The Factor VIII-related antigen (FVIII) expression observed in endothelial cells cytoplasm corresponding to sprouts in the CT and P regions from GITC could indicate the occurrence of early angiogenesis events in these tumors
Summary
The importance of tumor angiogenesis in the growth, progression and metastasis of solid tumors is widely known. Blood vessels are recruited by tumors from the neighboring tissues by this process, in which a plethora of angiogenic factors are involved [1]. It is known that the tumor growth and metastasis depend on distinct biological properties of cancer cells, and in multiple and complex tumor microenvironment interaction with the host cells and factors that maintain the tissues homeostasis [3]. Since the last decade translational cancer biology has evolved with the prolific research addressing the clinical implications of angiogenic response, quantitated or in relation with prognosis, and the role of inhibitory molecules/factors to slow the tumor proliferation. The number and distribution of blood vessels in different regions of tumors might be relevant for tumor growth and metastasis, delivery of anti-neoplastic drugs, radiotherapy effectiveness, clinic outcome and prognosis [4,5]. In the last two decades, the increased MVD has been associated with early progression in several tumors including the gastrointestinal cancer [7]
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