Human umbilical cord mesenchymal stem cells promote carcinoma growth and lymph node metastasis when co-injected with esophageal carcinoma cells in nude mice

Abstract

BackgroundHuman umbilical cord blood derived-mesenchymal stem cells (hUCMSCs) offer an attractive alternative to bone marrow-derived MSCs (BMMSCs) for cell-based therapy as it is a less invasive source of biological material. However, limited studies have been conducted with hUCMSCs as compared to BMMSCs. The present study was conducted to evaluate the effects of hUCMSCs in esophageal carcinoma (EC).MethodshUCMSCs together with EC cells were transplanted subcutaneously into BALB/c nude mice to observe the effects of hUCMSCs on tumor establishment. hUCMSCs injected through the caudal vein to the mice with pre-established EC to observe the effects of hUCMSCs on tumor outgrowth. In order to elucidate the underlying mechanisms, we also performed in vitro experiments including directly co-culture, transwell assay, proliferation assay and western blotting analysis.ResultshUCMSCs promoted EC formation in nude mice. In the in vivo model of pre-established EC, intravenously injected hUCMSCs potently promoted tumor growth. When in vitro co-cultured with hUCMSCs, EC cells proliferation increased. After co-cultured with hUCMSCs through transwell system, EC cells showed increased proliferation. Through transwell assay, we also observed that EC cells recruited MSCs, and MSCs promoted EC cells migration and invasion. Western blotting data showed that the expressions of proliferation related proteins Bcl-2, survivin and metastasis related proteins MMP-2 and MMP-9 were up-regulated in the EC cells transwell co-cultured with hUCMSCs.ConclusionsOur results indicated that hUCMSCs could favor tumor growth in vivo and in vitro. Thus, the exploitation of hUCMSCs in new therapeutic strategies should be cautious under the malignant conditions.

Wharton’s Jelly‐Derived Mesenchymal Stromal Cells and Fibroblast‐Derived Extracellular Matrix Synergistically Activate Apoptosis in a p21‐Dependent Mechanism in WHCO1 and MDA MB 231 Cancer Cells In Vitro

“…Its downregulation together with Bcl-xL, MMP-2, MMP-9, and cyclin D1 provides a pathway through which proliferation is inhibited and apoptosis is induced. It has been shown that human umbilical cord mesenchymal stromal cells promote carcinoma growth when coinjected with esophageal carcinoma cells in nude mice [ 68 , 69 ]. Their results differ from those reported in this in vitro study.…”

“…Another explanation could be that cancer cells secrete many chemokines such as IL6 and IL8 and can stimulate migration in cancer cells; thus, the decreased IL6 and IL8 expression observed in this study (data not shown) suggest that it is associated with the decrease in cancer survival genes such as BCL-2, BCL-XL, MMP-2, and MMP-9 . MMP-2 and MMP-9 are the two most important proteins associated with tumour cell invasion and metastasis [ 68 , 69 ]. We observed in this study that both MMP-2 and MMP-9 protein levels and activity are downregulated in the presence of WJ-MSCs and fd-ECM, clearly showing that both MSCs and fd-ECM have an effect on “cancer survival” genes.…”

Wharton’s Jelly Derived Mesenchymal Stem Cells: Future of Regenerative Medicine? Recent Findings and Clinical Significance

“…Still, we must undertake far-reaching precautions and moderate enthusiasm in the implementation of WJ-MSC as anticancer therapy, since reports of tumor supporting function were recently published in regard to esophageal carcinoma [ 79 ] and renal cancer [ 80 ].…”

Mesenchymal Stem Cells: How Can we Realize their Therapeutic Potential in Cancer Therapy?

“…An increase in metastatic characteristics was seen in MDA-MB-231 breast cancer cells in an orthotopic mouse model [20], esophageal cell lines TE-1 and Eca109 in vitro and in vivo [14] and A549 lung cancer cells [21].…”

“…MSCs were shown to increase initiation and growth rates of a variety of tumour types including gastric cancer [13], esophageal cancer [14] and MCF7/Ras breast cancer [4], generally through the secretion of anti-apoptotic and pro-proliferative cytokines, for example via production of CCL5 (RANTES) and interleukin-6 in breast cancer models ( [4,15] and see Zimmerlin et al [16] for a more complete list of cytokines). It is also possible that cytokines found to be produced by MSCs in non-cancerous situations, for example, in wound healing, hematopoiesis and arteriogenesis, might also be secreted in cancer [17][18][19].…”