TY - JOUR
T1 - Mesenchymal stem cell secretome and regenerative therapy after cancer
AU - Zimmerlin, Ludovic
AU - Park, Tea Soon
AU - Zambidis, Elias T.
AU - Donnenberg, Vera S.
AU - Donnenberg, Albert D.
N1 - Funding Information:
Drs. Albert and Vera Donnenberg were supported by grants BC032981 and BC044784 from the Department of Defense , grant R01CA 114246 from the NIH , grant R01-HL-085819 from the National Heart, Lung, and Blood Institute , the Hillman Foundation , the Glimmer of Hope Foundation , the Commonwealth of Pennsylvania , through the McGowan Institute of Regenerative Medicine, the NHLBI (Production Assistance for Cellular Therapy (PACT) N01-HB-37165), and the Department of Defense Biomedical Translational Initiative (W911QY-09-C-0209). Drs. Donnenberg would also like to thank Diana Napper from The Glimmer of Hope Foundation for her support. Dr. Zambidis and Dr. Park were supported by grants from NIH 1U01HL099775 and U01HL100397 (ETZ) and the Maryland Stem Cell Research Fund : 2011-MS CRF II-0008-00 and 2007-MSCRF II-0379-00 (ETZ), and the Maryland Stem Cell Research Fund (MSCFR) Postdoctoral Fellowship grant 2009-MSCRF III-106570 (TSP).
PY - 2013/12
Y1 - 2013/12
N2 - Cancer treatment generally relies on tumor ablative techniques that can lead to major functional or disfiguring defects. These post-therapy impairments require the development of safe regenerative therapy strategies during cancer remission. Many current tissue repair approaches exploit paracrine (immunomodulatory, pro-angiogenic, anti-apoptotic and pro-survival effects) or restoring (functional or structural tissue repair) properties of mesenchymal stem/stromal cells (MSC). Yet, a major concern in the application of regenerative therapies during cancer remission remains the possible triggering of cancer recurrence. Tumor relapse implies the persistence of rare subsets of tumor-initiating cancer cells which can escape anti-cancer therapies and lie dormant in specific niches awaiting reactivation via unknown stimuli. Many of the components required for successful regenerative therapy (revascularization, immunosuppression, cellular homing, tissue growth promotion) are also critical for tumor progression and metastasis. While bi-directional crosstalk between tumorigenic cells (especially aggressive cancer cell lines) and MSC (including tumor stroma-resident populations) has been demonstrated in a variety of cancers, the effects of local or systemic MSC delivery for regenerative purposes on persisting cancer cells during remission remain controversial. Both pro- and anti-tumorigenic effects of MSC have been reported in the literature. Our own data using breast cancer clinical isolates have suggested that dormant-like tumor-initiating cells do not respond to MSC signals, unlike actively dividing cancer cells which benefited from the presence of supportive MSC. The secretome of MSC isolated from various tissues may partially diverge, but it includes a core of cytokines (i.e. CCL2, CCL5, IL-6, TGFβ, VEGF), which have been implicated in tumor growth and/or metastasis. This article reviews published models for studying interactions between MSC and cancer cells with a focus on the impact of MSC secretome on cancer cell activity, and discusses the implications for regenerative therapy after cancer.
AB - Cancer treatment generally relies on tumor ablative techniques that can lead to major functional or disfiguring defects. These post-therapy impairments require the development of safe regenerative therapy strategies during cancer remission. Many current tissue repair approaches exploit paracrine (immunomodulatory, pro-angiogenic, anti-apoptotic and pro-survival effects) or restoring (functional or structural tissue repair) properties of mesenchymal stem/stromal cells (MSC). Yet, a major concern in the application of regenerative therapies during cancer remission remains the possible triggering of cancer recurrence. Tumor relapse implies the persistence of rare subsets of tumor-initiating cancer cells which can escape anti-cancer therapies and lie dormant in specific niches awaiting reactivation via unknown stimuli. Many of the components required for successful regenerative therapy (revascularization, immunosuppression, cellular homing, tissue growth promotion) are also critical for tumor progression and metastasis. While bi-directional crosstalk between tumorigenic cells (especially aggressive cancer cell lines) and MSC (including tumor stroma-resident populations) has been demonstrated in a variety of cancers, the effects of local or systemic MSC delivery for regenerative purposes on persisting cancer cells during remission remain controversial. Both pro- and anti-tumorigenic effects of MSC have been reported in the literature. Our own data using breast cancer clinical isolates have suggested that dormant-like tumor-initiating cells do not respond to MSC signals, unlike actively dividing cancer cells which benefited from the presence of supportive MSC. The secretome of MSC isolated from various tissues may partially diverge, but it includes a core of cytokines (i.e. CCL2, CCL5, IL-6, TGFβ, VEGF), which have been implicated in tumor growth and/or metastasis. This article reviews published models for studying interactions between MSC and cancer cells with a focus on the impact of MSC secretome on cancer cell activity, and discusses the implications for regenerative therapy after cancer.
KW - Cancer recurrence
KW - Mesenchymal stem/stromal cells
KW - Regenerative therapy after cancer
KW - Tumor-initiating cells
UR - http://www.scopus.com/inward/record.url?scp=84887821937&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84887821937&partnerID=8YFLogxK
U2 - 10.1016/j.biochi.2013.05.010
DO - 10.1016/j.biochi.2013.05.010
M3 - Short survey
C2 - 23747841
AN - SCOPUS:84887821937
SN - 0300-9084
VL - 95
SP - 2235
EP - 2245
JO - Biochimie
JF - Biochimie
IS - 12
ER -