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Myeloid-Specific Expression of Ron Receptor Kinase Promotes Prostate Tumor Growth

Ron receptor kinase (MST1R) is important in promoting epithelial tumorigenesis, but the potential contributions of its specific expression in stromal cells have not been examined. Herein, we show that the Ron receptor is expressed in mouse and human stromal cells of the prostate tumor microenvironme...

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Published in:Cancer research (Chicago, Ill.) Ill.), 2013-03, Vol.73 (6), p.1752-1763
Main Authors: GURUSAMY, Devikala, GRAY, Jerilyn K, PATHROSE, Peterson, KULKARNI, Rishikesh M, FINKLEMAN, Fred D, WALTZ, Susan E
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cited_by cdi_FETCH-LOGICAL-c507t-eca04b944857eedaf5d71c5c2cd2956b282ba6f2267f855e4d77be89031be5553
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container_title Cancer research (Chicago, Ill.)
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creator GURUSAMY, Devikala
GRAY, Jerilyn K
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FINKLEMAN, Fred D
WALTZ, Susan E
description Ron receptor kinase (MST1R) is important in promoting epithelial tumorigenesis, but the potential contributions of its specific expression in stromal cells have not been examined. Herein, we show that the Ron receptor is expressed in mouse and human stromal cells of the prostate tumor microenvironment. To test the significance of stromal Ron expression, prostate cancer cells were orthotopically implanted into the prostates of either wild-type or Ron tyrosine kinase deficient (TK(-/-); Mst1r(-/-)) hosts. In TK(-/-) hosts, prostate cancer cell growth was significantly reduced as compared with tumor growth in TK(+/+) hosts. Prostate tumors in TK(-/-) hosts exhibited an increase in tumor cell apoptosis, macrophage infiltration and altered cytokine expression. Reciprocal bone marrow transplantation studies and myeloid cell-specific ablation of Ron showed that loss of Ron in myeloid cells is sufficient to inhibit prostate cancer cell growth. Interestingly, depletion of CD8(+) T cells, but not CD4(+) T cells, was able to restore prostate tumor growth in hosts devoid of myeloid-specific Ron expression. These studies show a critical role for the Ron receptor in the tumor microenvironment, whereby Ron loss in tumor-associated macrophages inhibits prostate cancer cell growth, at least in part, by derepressing the activity of CD8(+) T cells.
doi_str_mv 10.1158/0008-5472.can-12-2474
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Drug treatments</subject><subject>Prostatic Neoplasms - enzymology</subject><subject>Prostatic Neoplasms - immunology</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Receptor Protein-Tyrosine Kinases - genetics</subject><subject>Receptor Protein-Tyrosine Kinases - physiology</subject><subject>Tumors</subject><subject>Tumors of the urinary system</subject><subject>Urinary tract. 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subjects Animals
Antineoplastic agents
Biological and medical sciences
CD8-Positive T-Lymphocytes - immunology
Cell Line, Tumor
Flow Cytometry
Gynecology. Andrology. Obstetrics
Immunohistochemistry
Male
Male genital diseases
Medical sciences
Mice
Mice, Knockout
Multiple tumors. Solid tumors. Tumors in childhood (general aspects)
Nephrology. Urinary tract diseases
Pharmacology. Drug treatments
Prostatic Neoplasms - enzymology
Prostatic Neoplasms - immunology
Prostatic Neoplasms - pathology
Real-Time Polymerase Chain Reaction
Receptor Protein-Tyrosine Kinases - genetics
Receptor Protein-Tyrosine Kinases - physiology
Tumors
Tumors of the urinary system
Urinary tract. Prostate gland
title Myeloid-Specific Expression of Ron Receptor Kinase Promotes Prostate Tumor Growth
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