Mast Cells Are Novel Independent Prognostic Markers in Prostate Cancer and Represent a Target for Therapy

Abstract

Mast cells affect growth in various humanCancer growth is dependent on the reciprocal interaction between tumor cells and their microenvironment. Cancerassociated fibroblasts, 1 vascular cells, and inflammatory cells such as macrophages [2][3][4] have been shown to promote prostate tumor growth. Mast cells are also of importance for tumor growth and have been shown to affect angiogenesis 5-7 but are also potent regulators of inflammation and thus their specific function during tumor progression is complex and shows significant plasticity. 8 -10 Their role in prostate cancer (PC) in patients was recently explored in two separate studies using tryptase and c-Kit as markers for mast cells. These studies lacked the discrepancy between intra-and peritumoral mast cells and did not identify mast cells as independent prognostic variables. One of the studies showed that tryptase-positive mast cells were related to poor outcome in PC patients. 12 The other study analyzed c-Kit-positive cells in tumor samples from PC patients and found an association between increased mast cell numbers and a favorable prognosis. 13Castration therapy is the gold standard for treatment of patients with metastatic PC, but in the majority of cases the formation of castrate-resistant prostate tumors is inevitable. The mechanisms behind the relapse are not fully understood but could be related to changes in the androgen receptor and the tumor stroma.

Prostate Cancer Increases Hyaluronan in Surrounding Nonmalignant Stroma, and This Response Is Associated with Tumor Growth and an Unfavorable Outcome

“…We have proposed that this type of prostate tissue can be termed TINT, and that prostate tissue is tinted in a particular way by the presence of aggressive tumors. 49 In line with this, in TINT stroma surrounding aggressive tumors the androgen receptors are decreased, 10 and mast cell numbers 16 and platelet-derived growth factor-receptor ␤ are increased. 17 In TINT epithelium surrounding aggressive tumors phosphorylated epidermal growth factor receptors and phosphorylated activated protein kinase is increased.…”

“…The androgen receptor and smooth muscle markers are decreased, 10 mast cells 16 and platelet-derived growth factor-receptor ␤ are increased, 17 and these alterations are related to prostate cancer death, and for androgen receptor these alterations also are related to a limited response to castration therapy. 10 The mechanisms explaining why the stroma is changed in prostate cancers and in the surrounding normal prostate tissue, and why this is related to disease aggressiveness and treatment outcome, are largely unknown.…”

Inhibition of Mast Cell-Derived Histamine Decreases Human Cholangiocarcinoma Growth and Differentiation via c-Kit/Stem Cell Factor–Dependent Signaling

“…42 Mast cells themselves may be a potential diagnostic marker for prostate cancer, although there is discrepancy among scientists about the definitive role of mast cells in prostate cancer. 43 Finally, our studies elucidate that targeting the c-Kit/SCF interaction may be a beneficial treatment option to diminish tumorigenesis and progression.…”

A Critical Role for Mast Cells and Mast Cell-Derived IL-6 in TLR2-Mediated Inhibition of Tumor Growth

“…1C). As the ability of mast cells to exert a protective role in tumorigenesis may be dependent on an intratumoral distribution (28,29), we assessed the distribution of mast cells in control and Pam 3 CSK 4 -treated tumors. Mast cells were predominately found in the stroma as opposed to intratumorally for both PBS-treated (2.3 6 0.5/mm 2 versus 0.5 6 0.1/mm 2 , n = 6) and Pam 3 CSK 4 -treated (3.3 6 0.7/mm 2 versus 1.7 6 0.9/mm 2 , n = 9) tumors.…”