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Recruitment of mesenchymal stem cells into prostate tumours promotes metastasis.

Jung Y, Kim JK, Shiozawa Y, Wang J, Mishra A, Joseph J, Berry JE, McGee S, Lee E, Sun H, Wang J, Jin T, Zhang H, Dai J, Krebsbach PH, Keller ET, Pienta KJ, Taichman RS - Nat Commun (2013)

Bottom Line: Here we show that CXCL16, a ligand for CXCR6, facilitates mesenchymal stem cell or very small embryonic-like cells recruitment into prostate tumours.CXCR6 signalling stimulates the conversion of mesenchymal stem cells into cancer-associated fibroblasts, which secrete stromal-derived factor-1, also known as CXCL12.CXCL12 expressed by cancer-associated fibroblasts then binds to CXCR4 on tumour cells and induces an epithelial-to-mesenchymal transition, which ultimately promotes metastasis to secondary tumour sites.

View Article: PubMed Central - PubMed

Affiliation: Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan 48109, USA.

ABSTRACT
Tumours recruit mesenchymal stem cells to facilitate healing, which induces their conversion into cancer-associated fibroblasts that facilitate metastasis. However, this process is poorly understood on the molecular level. Here we show that CXCL16, a ligand for CXCR6, facilitates mesenchymal stem cell or very small embryonic-like cells recruitment into prostate tumours. CXCR6 signalling stimulates the conversion of mesenchymal stem cells into cancer-associated fibroblasts, which secrete stromal-derived factor-1, also known as CXCL12. CXCL12 expressed by cancer-associated fibroblasts then binds to CXCR4 on tumour cells and induces an epithelial-to-mesenchymal transition, which ultimately promotes metastasis to secondary tumour sites. Our results provide the molecular basis for mesenchymal stem cell recruitment into tumours and how this process leads to tumour metastasis.

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Bone marrow-derived MSCs promote prostate cancer growth and metastasisModel showing putative potential mechanisms underlying primary prostate cancer progression by the recruitment of mescenchymal cells (MSCs) and bone metastasis. Secretion of CXCL16 by cancer cells recruits MSCs into tumor sites. Tumor-derived CXCL16 interacts with its receptor, CXCR6 on MSCs and activates signal transduction, leading MSCs to convert into cancer-associated fibroblasts (CAFs), which secrete the high levels of CXCL12. CXCL12 promotes the malignant transformation of proliferating cancer cells to an epithelial-mesenchymal transition (EMT). EMT enhances CXCR4 expression in prostate cancer cells. CXCR4 expression facilitates metastasis.
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Figure 6: Bone marrow-derived MSCs promote prostate cancer growth and metastasisModel showing putative potential mechanisms underlying primary prostate cancer progression by the recruitment of mescenchymal cells (MSCs) and bone metastasis. Secretion of CXCL16 by cancer cells recruits MSCs into tumor sites. Tumor-derived CXCL16 interacts with its receptor, CXCR6 on MSCs and activates signal transduction, leading MSCs to convert into cancer-associated fibroblasts (CAFs), which secrete the high levels of CXCL12. CXCL12 promotes the malignant transformation of proliferating cancer cells to an epithelial-mesenchymal transition (EMT). EMT enhances CXCR4 expression in prostate cancer cells. CXCR4 expression facilitates metastasis.

Mentions: MSCs are multipotent cells that contribute to tissue homeostasis and regeneration. Tumors recruit MSCs to facilitate tumor progression and metastasis. Here, we provide evidence that the recruitment of MSCs into prostate cancer is dependent on the expression of the CXCR6 ligand, CXCL16 by tumor cells (Fig. 6). CXCR6 signaling supports the recruitment, conversion and activation of MSC into CXCL12 secreting CAFs. Moreover, enhanced CXCL12 secretion supports an EMT conversion of the prostate cancer cells and an increase in the expression of the CXCL12 receptor, CXCR4. These events result in enhanced tumor progression and ultimately extravasation and metastasis. Targeting MSCs and the CXCL16/CXCR6 axis may prevent tumor progression and metastasis of prostate cancer and provide a more effective therapeutic strategy for prostate cancer.


Recruitment of mesenchymal stem cells into prostate tumours promotes metastasis.

Jung Y, Kim JK, Shiozawa Y, Wang J, Mishra A, Joseph J, Berry JE, McGee S, Lee E, Sun H, Wang J, Jin T, Zhang H, Dai J, Krebsbach PH, Keller ET, Pienta KJ, Taichman RS - Nat Commun (2013)

Bone marrow-derived MSCs promote prostate cancer growth and metastasisModel showing putative potential mechanisms underlying primary prostate cancer progression by the recruitment of mescenchymal cells (MSCs) and bone metastasis. Secretion of CXCL16 by cancer cells recruits MSCs into tumor sites. Tumor-derived CXCL16 interacts with its receptor, CXCR6 on MSCs and activates signal transduction, leading MSCs to convert into cancer-associated fibroblasts (CAFs), which secrete the high levels of CXCL12. CXCL12 promotes the malignant transformation of proliferating cancer cells to an epithelial-mesenchymal transition (EMT). EMT enhances CXCR4 expression in prostate cancer cells. CXCR4 expression facilitates metastasis.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3649763&req=5

Figure 6: Bone marrow-derived MSCs promote prostate cancer growth and metastasisModel showing putative potential mechanisms underlying primary prostate cancer progression by the recruitment of mescenchymal cells (MSCs) and bone metastasis. Secretion of CXCL16 by cancer cells recruits MSCs into tumor sites. Tumor-derived CXCL16 interacts with its receptor, CXCR6 on MSCs and activates signal transduction, leading MSCs to convert into cancer-associated fibroblasts (CAFs), which secrete the high levels of CXCL12. CXCL12 promotes the malignant transformation of proliferating cancer cells to an epithelial-mesenchymal transition (EMT). EMT enhances CXCR4 expression in prostate cancer cells. CXCR4 expression facilitates metastasis.
Mentions: MSCs are multipotent cells that contribute to tissue homeostasis and regeneration. Tumors recruit MSCs to facilitate tumor progression and metastasis. Here, we provide evidence that the recruitment of MSCs into prostate cancer is dependent on the expression of the CXCR6 ligand, CXCL16 by tumor cells (Fig. 6). CXCR6 signaling supports the recruitment, conversion and activation of MSC into CXCL12 secreting CAFs. Moreover, enhanced CXCL12 secretion supports an EMT conversion of the prostate cancer cells and an increase in the expression of the CXCL12 receptor, CXCR4. These events result in enhanced tumor progression and ultimately extravasation and metastasis. Targeting MSCs and the CXCL16/CXCR6 axis may prevent tumor progression and metastasis of prostate cancer and provide a more effective therapeutic strategy for prostate cancer.

Bottom Line: Here we show that CXCL16, a ligand for CXCR6, facilitates mesenchymal stem cell or very small embryonic-like cells recruitment into prostate tumours.CXCR6 signalling stimulates the conversion of mesenchymal stem cells into cancer-associated fibroblasts, which secrete stromal-derived factor-1, also known as CXCL12.CXCL12 expressed by cancer-associated fibroblasts then binds to CXCR4 on tumour cells and induces an epithelial-to-mesenchymal transition, which ultimately promotes metastasis to secondary tumour sites.

View Article: PubMed Central - PubMed

Affiliation: Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan 48109, USA.

ABSTRACT
Tumours recruit mesenchymal stem cells to facilitate healing, which induces their conversion into cancer-associated fibroblasts that facilitate metastasis. However, this process is poorly understood on the molecular level. Here we show that CXCL16, a ligand for CXCR6, facilitates mesenchymal stem cell or very small embryonic-like cells recruitment into prostate tumours. CXCR6 signalling stimulates the conversion of mesenchymal stem cells into cancer-associated fibroblasts, which secrete stromal-derived factor-1, also known as CXCL12. CXCL12 expressed by cancer-associated fibroblasts then binds to CXCR4 on tumour cells and induces an epithelial-to-mesenchymal transition, which ultimately promotes metastasis to secondary tumour sites. Our results provide the molecular basis for mesenchymal stem cell recruitment into tumours and how this process leads to tumour metastasis.

Show MeSH
Related in: MedlinePlus