Tumor–Microenvironment Interaction: Analysis of Mast Cell Populations in Normal Tissue and Proliferative Disorders of the Canine Prostate

Abstract

Mast cells (MCs) are involved in angiogenesis, tissue remodeling and immunomodulation in several human and animal tumors, although their exact role is still controversial. Since no information is available in canine prostate carcinoma (PC) and normal prostate tissues, the aims of this study were to evaluate the possible correlations between MC distribution, molecular expression and microvessel density (MVD) in normal prostatic tissue and proliferative disorders of the canine prostate. All samples (6 normal, 15 benign prostate hyperplasia-BPH, 8 PC) were stained with Toluidine Blue and immunohistochemically evaluated for tryptase, c-Kit (CD117) and CD31. Mast cell density (MCD) and MVD were quantified by the hot-spot method. MCD was significantly increased in periglandular/peritumoral areas, when compared with intraglandular/intratumoral areas, in all groups (p = 0.03). C-Kit expression was strongly associated with PC (ρ = 0.75 p = 0.03), whereas positive correlation between tryptase and c-Kit expression (ρ = 0.64 p = 0.01) was observed in periglandular areas of BPH. MVD showed a correlation with MCD in BPH (ρ = 0.54 p = 0.04). Our data support the importance of c-Kit in regulating MC proliferation. The predominant location of MCs in peritumoral areas of canine PC was similar to the human counterpart, in which PC cells are supposed to produce substances attracting MCs to the tumor microenvironment.

Comparative Pathobiology of Canine and Human Prostate Cancer: State of the Art and Future Directions

“…Mechanisms of mast cell recruitment in the tumor microenvironment were evidenced when using human PC cell lines, contributing to the neoformation of blood vessels [ 196 ]. This tumor-microenvironment interaction was also observed by Defourny et al [ 121 ]. According to the authors, canine PC lesions have a high density of mast cells with periglandular/peritumoral distribution.…”

“…In addition to its role in regulating cell proliferation, c-KIT appears to be involved in regulating the survival and activation of mast cells, cells involved in tumor-microenvironment interaction in the canine PC [ 121 ]. In humans, normal prostate peripheral stromal cells have been associated with the development of PC through the c-KIT signaling pathway [ 122 ], reinforcing the findings by Fonseca-Alves et al [ 110 ].…”

“…According to the authors, canine PC lesions have a high density of mast cells with periglandular/peritumoral distribution. However, unlike men, there is no positive correlation between tryptase, one of the serine proteases secreted by mast cells, and the higher density of microvessels in PC in dogs, requiring the investigation of other pro-angiogenic proteases [ 121 ].…”

La inflamación y su relación con el cáncer

“…Los principales efectores antitumorales son los linfocitos T CD8+, en contraste con los linfocitos T CD4+ que tienden a asociarse con inmunosupresión, aunque estos últimos tienen la capacidad de regular ambos estados. Adicionalmente, una subpoblación de linfocitos T reguladores con fenotipo CD4+, CD25+, FOXP3+, también conocidos como linfocitos Treg, han adquirido relevancia por su actividad altamente inmunosupresora (Defourny et al, 2019). Los Tregs pueden inducir la conversión de linfocitos T CD4+ a fenotipo supresor a través de la secreción particular de TGF-β.…”