Journal
MOLECULAR & CELLULAR PROTEOMICS
Volume 14, Issue 3, Pages 471-483Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/mcp.M114.039909
Keywords
-
Categories
Funding
- Cancer Prevention and Research Institute of Texas [CPRIT RP110327]
- National Institutes of Health [RO1 174798, P50-CA140388, 1S10RR020923]
- US Department of Defense [PC093132]
- Prostate Cancer Foundation
- Cancer Center Support grant from the National Cancer Institute [2P30CA016647]
- European Union FP7-PEOPLE-IAPP- [324400 - GlycoMet]
- National Science Foundation EPSCoR [1004057]
- Rhode Island Science and Technology Advisory Council grant
- Division of Biology and Medicine, Brown University
Ask authors/readers for more resources
A distinct feature of human prostate cancer (PCa) is the development of osteoblastic (bone-forming) bone metastases. Metastatic growth in the bone is supported by factors secreted by PCa cells that activate signaling networks in the tumor microenvironment that augment tumor growth. To better understand these signaling networks and identify potential targets for therapy of bone metastases, we characterized the secretome of a patient-derived xenograft, MDA-PCa-118b (PCa-118b), generated from osteoblastic bone lesion. PCa-118b induces osteoblastic tumors when implanted either in mouse femurs or subcutaneously. To study signaling molecules critical to these unique tumor/microenvironment-mediated events, we performed mass spectrometry on conditioned media of isolated PCa-118b tumor cells, and identified 26 secretory proteins, such as TGF-beta 2, GDF15, FGF3, FGF19, CXCL1, galectins, and beta 2-microglobulin, which represent both novel and previously published secreted proteins. RT-PCR using human versus mouse-specific primers showed that TGF beta 2, GDF15, FGF3, FGF19, and CXCL1 were secreted from PCa-118b cells. TGF beta 2, GDF15, FGF3, and FGF19 function as both autocrine and paracrine factors on tumor cells and stromal cells, that is, endothelial cells and osteoblasts. In contrast, CXCL1 functions as a paracrine factor through the CXCR2 receptor expressed on endothelial cells and osteoblasts. Thus, our study reveals a complex PCa bone metastasis secretome with paracrine and autocrine signaling functions that mediate cross-talk among multiple cell types within the tumor microenvironment.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available