Quantification of Mesenchymal Stem Cells (MSCs) at sites of human prostate cancer

Research output: Contribution to journalArticle

Abstract

Circulating bone marrow-derived Mesenchymal Stem Cells (BM-MSCs) have an innate tropism for tumor tissue in response to the inflammatory microenvironment present in malignant lesions. The prostate is bombarded by numerous infectious & inflammatory insults over a lifetime. Chronic inflammation is associated with CXCL12, CCL5, and CCL2, which are highly overexpressed in prostate cancer. Among other cell types, these chemoattractant stimuli recruit BM-MSCs to the tumor. MSCs are minimally defined as plastic-adhering cells characterized by the expression of CD90, CD73, and CD105 in the absence of hematopoietic markers, which can differentiate into osteoblasts, chondrocytes, and adipocytes. MSCs are immunoprivileged and have been implicated in tumorigenesis through multiple mechanisms, including promoting proliferation, angiogenesis, and metastasis, in addition to the generation of an immunosuppressive microenvironment. We have demonstrated that MSCs represent 0.01-1.1% of the total cells present in core biopsies from primary human prostatectomies. Importantly, these analyses were performed on samples prior to expansion in tissue culture. MSCs in these prostatectomy samples are FAP-, CD90-, CD73-, and CD105-positive, and CD14-, CD20-, CD34-, CD45-, and HLA-DR-negative. Additionally, like BM-MSCs, these prostate cancer-derived stromal cells (PrCSCs) were shown to differentiate into osteoblasts, adipocytes, & chondrocytes. In contrast to primary prostate cancer-derived epithelial cells, fluorescently-labeled PrCSCs & BMMSCs were both shown to home to CWR22RH prostate cancer xenografts following IV injection. These studies demonstrate that not only are MSCs present in sites of prostate cancer where they may contribute to carcinogenesis, but these cells may also potentially be used to deliver cytotoxic or imaging agents for therapeutic and/or diagnostic purposes.

Original languageEnglish (US)
Pages (from-to)106-117
Number of pages12
JournalOncotarget
Volume4
Issue number1
StatePublished - 2013

Fingerprint

Mesenchymal Stromal Cells
Prostatic Neoplasms
Bone Marrow
Stromal Cells
Prostatectomy
Chondrocytes
Osteoblasts
Adipocytes
Carcinogenesis
Tissue Expansion
Tropism
Chemotactic Factors
HLA-DR Antigens
Immunosuppressive Agents
Heterografts
Plastics
Prostate
Neoplasms
Epithelial Cells
Neoplasm Metastasis

Keywords

  • CAF
  • Drug delivery
  • Inflammation
  • Mesenchymal stem cells
  • MSC
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology

Cite this

Quantification of Mesenchymal Stem Cells (MSCs) at sites of human prostate cancer. / Brennen, William; Chen, Shuangling; Denmeade, Samuel R; Isaacs, John Tod.

In: Oncotarget, Vol. 4, No. 1, 2013, p. 106-117.

Research output: Contribution to journalArticle

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