Adult human mesenchymal stem cells enhance breast tumorigenesis and promote hormone independence

Rhodes, Lyndsay V.; Muir, Shannon E.; Elliott, Steven; Guillot, Lori M.; Antoon, James W.; Penfornis, Patrice; Tilghman, Syreeta L.; Salvo, Virgilio A.; Fonseca, Juan P.; Lacey, Michelle; Beckman, Barbara S.; McLachlan, John A.; Rowan, Brian G.; Pochampally, Radhika; Burow, Matthew E.

doi:10.1007/s10549-009-0458-2

Cited by 97 publications

(77 citation statements)

References 26 publications

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“…The MDA-MB-231 and MDA-MB-468 cell lines (human breast cancer negative for ER, PR and Her2/neu) were acquired from the American Type Culture Collection (Manassas, VA, USA) and cultured as previously described (22)(23)(24). Glyceollin mixture was isolated as previously described (22).…”

Section: Cells and Reagentsmentioning

confidence: 99%

Glyceollins as novel targeted therapeutic for the treatment of triple-negative breast cancer

et al. 2011

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Abstract. The purpose of this study was to investigate the effects of glyceollins on the suppression of tumorigenesis in triple-negative breast carcinoma cell lines. We further explored the effects of glyceollins on microRNA and protein expression in MDA-MB-231 cells. Triple-negative (ER-, PgR-and Her2/ neu-) breast carcinoma cells were used to test the effects of glyceollins on tumorigenesis in vivo. Following this procedure, unbiased microarray analysis of microRNA expression was performed. Additionally, we examined the changes in the proteome induced by glyceollins in the MDA-MB-231 cells. Tumorigenesis studies revealed a modest suppression of MDA-MB-231 and MDA-MB-468 cell tumor growth in vivo. In response to glyceollins we observed a distinct change in microRNA expression profiles and proteomes of the triple-negative breast carcinoma cell line, MDA-MB-231. Our results demonstrated that the glyceollins, previously described as anti-estrogenic agents, also exert antitumor activity in triple-negative breast carcinoma cell systems. This activity correlates with the glyceollin alteration of microRNA and proteomic expression profiles.

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Section: Cells and Reagentsmentioning

confidence: 99%

Glyceollins as novel targeted therapeutic for the treatment of triple-negative breast cancer

et al. 2011

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“…Some studies show tumor progression and enhancement of tumor metastatic potential by hMSC. Such tumor progression is induced by cell-cell contact as well as by the secretion of several cytokines and growth factors [Karnoub et al, 2007;Lin et al 2008;Rhodes et al, 2010]. In contrast, there are also reports of cancer inhibition and induction of apoptosis by hMSC [Khakoo et al, 2006;Zhu et al, 2009].…”

Section: Introductionmentioning

confidence: 99%

Human Mesenchymal Stem Cells Promote Cancer Motility and Cytokine Secretion in vitro

Scherzed

Hackenberg

Radeloff

et al. 2013

Cells Tissues Organs

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Interactions of human mesenchymal stem cells (hMSC) with tumors are controversially discussed since there is evidence for both tumor progression as well as tumor inhibition by hMSC. The objective of the present study is to investigate whether hMSC support cell motility and cytokine secretion in a head and neck squamous cell carcinoma cell line (HLaC 78). A spheroid model was generated in which the ultrastructure of spheroids was analyzed using scanning electron microscopy (SEM). The migration capability was monitored in a monolayer as well as in a spheroid model. The variation in migration and secretion of interleukin (IL)-6, IL-8 and vascular endothelial growth factor (VEGF), as well as the expression of the multidrug resistance gene (MDR-1) was investigated. Finally, the alteration in the cell cycle was analyzed by flow cytometry. SEM showed a tight cell-cell contact with extensive secretion of extracellular matrix. The migration and invasion capability of HLaC 78 was enhanced by hMSC. Cancer cell motility was also increased by hMSC as well as secretion of the cytokines IL-6, IL-8 and VEGF. hMSC did not induce the expression of MDR-1 in HLaC 78, and there was no alteration in the cell cycle of HLaC 78 after cocultivation with hMSC. Our results confirm the important role of hMSC in cancer biology since both an enhancement of cell motility as well as cytokine secretion could be shown. However, based on these findings and those in the current literature, caution must be applied when using hMSC as a carrier for tumor therapy in cancer treatment.

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“…Ahmad et al described the importance of the microenvironmental influence of adipose-derived mesenchymal stromal cells, including nuclear factor kappa β regulation of angiogenesis and invasion, 32 whereas Chaturvedi et al could show a hypoxia inducible factor-1α-dependent potential of mesenchymal stem cells to promote breast cancer progression and metastasis 33 as reflected by SDF-1/CXCR4 regulation. 17,34 Although adipose-derived mesenchymal stromal cells have been shown to have high regenerative potential and express high levels of vascular growth factors, we observed down-regulation of PDGF and Tie-2 in cancer tissue samples. Even though solid tumors and metastases developed (which depends on sufficient vascularity), interestingly, these vascular factors were not supportively up-regulated.…”

Section: Discussionmentioning

confidence: 70%

Human Adipose-Derived Mesenchymal Stromal Cells May Promote Breast Cancer Progression and Metastatic Spread

Kamat

Schweizer

Kaenel

et al. 2015

Plastic and Reconstructive Surgery

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BACKGROUND: Stem cell-enriched fat grafting has been proposed as a potential therapy for reconstructive, restorative, or enhancement-related procedures of the breast. Its role in postoncologic breast reconstruction is still emerging, with concerns about safety. The authors investigated the dose-dependent interaction between human adipose-derived mesenchymal stromal cells (AD-MSCs) and human breast cancer cell (BCC) lines [MDA-MB-231 (MDA) and MCF-7 (MCF)] focusing on tumor microenvironment, tumor growth, and metastatic spread. METHODS: Adipose-derived mesenchymal stromal cell influence on viability and factor expression [regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor-, and eotaxin) of breast cancer cells was studied in vitro using direct and indirect co-culture systems. Groups were formed according to adipose-derived mesenchymal stromal cell-to-cancer cell number ratio [MDA/MCF only, AD-MSC/(MDA/MCF), and AD-MSC/(MDA/MCF)]. A humanized orthotopic murine cancer model was used to evaluate breast cancer progression and metastasis (n = 10/group). Cells were injected into the mammary pad in different ratios and animals were monitored over 42 days. Microdialysis was performed to analyze RANTES levels in the tumor microenvironment (days 21 and 42). Primary and metastatic tumors were weighed and analyzed for oncogene, growth factor, and metastatic marker expression. RESULTS: MDA cell viability increased from 45.5 percent to 95.5 percent in presence of adipose-derived mesenchymal stromal cells in vitro. In vivo, animals with AD-MSC showed increased mean tumor weight (MDA, p < 0.01; MCF versus controls, p < 0.05) and metastatic occurrence (40 percent in MDA; 30 percent in MCF versus 0 percent in controls). Cytokine analysis revealed switching of MCF tumor phenotype to a more malignant type in the presence of adipose-derived mesenchymal stromal cells. CONCLUSION: Human adipose-derived mesenchymal stromal cells may promote progression and metastatic spread in breast cancer through a switch to a more malignant phenotype with worse prognosis. Methods: Adipose-derived mesenchymal stromal cell influence on viability and factor expression [regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor-α, and eotaxin) of breast cancer cells was studied in vitro using direct and indirect co-culture systems. Groups were formed according to adipose-derived mesenchymal stromal cell-to-cancer cell number ratio [MDA/MCF only, AD-MSC

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Adult human mesenchymal stem cells enhance breast tumorigenesis and promote hormone independence

Cited by 97 publications

References 26 publications

Glyceollins as novel targeted therapeutic for the treatment of triple-negative breast cancer

Glyceollins as novel targeted therapeutic for the treatment of triple-negative breast cancer

Human Mesenchymal Stem Cells Promote Cancer Motility and Cytokine Secretion in vitro

Human Adipose-Derived Mesenchymal Stromal Cells May Promote Breast Cancer Progression and Metastatic Spread

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