间充质干细胞在癌症治疗中的应用潜能

doi:10.3969/j.issn.1674-490X.2015.05.023

摘要/Abstract

摘要： 干细胞在恶性肿瘤中的应用受到越来越多的研究与探讨。间充质干细胞具有天然免疫豁免特性、向肿瘤细胞迁移的能力、多系分化的潜能，使其成为抗肿瘤的一种生物制剂。在肿瘤生长微环境下，间充质干细胞具有双重作用：促肿瘤形成和抗肿瘤形成。哪种作用占优势，取决于间充质干细胞的类型及来源，肿瘤细胞的类型，干细胞与机体免疫细胞、癌细胞的相互作用等。间充质干细胞分泌的肿瘤坏死因子相关凋亡诱导配体具有促进肿瘤细胞凋亡的作用。脐带组织来源的间充质干细胞与癌细胞共培养，可促进干细胞表达该配体，具有抗肿瘤作用。对间充质干细胞的促肿瘤形成和抗肿瘤形成的特性进行综述。

关键词: 间充质干细胞, 肿瘤, 趋向性, 抗癌

Abstract: Stem cell treatments are being increasingly explored for their possible potential to treat various cancers. Mesenchymal stem cells are believed to possess anti-tumor potential and are preferred for their properties like immune privileged nature, ability to migrate to the site of tumor and capability for multilineage differentiation. This tumor tropism property of MSCs could be utilized to deliver anti-tumor biological agents to the site of tumor. In a tumor micro-environment, MSCs are believed to play both, a pro-tumorigenic and an anti-tumorigenic role. However, this is dependent on a host of factors like, types of MSCs, its source, type of cancer cell line under investigation, interactions between MSCs, host’s immune cells and cancer cells. Among several cytokines secreted by MSCs, TRAIL (Tumor necrosis factor related apoptosis inducing ligand) are reported to be pro-apoptotic for tumor cells. Umbilical cord tissue derived MSCs are believed to regulate TRAIL expression in MSC-cancer cell co-culture system resulting in induction of apoptosis in cancer cells. We present a review concerning on pro-tumorigenic and anti-tumorigenic properties of MSCs based on different studies reporting.

Key words: mesenchymal stem cells, tumor, tropism, anti-cancer

中图分类号:

瞿海龙，梁璐，边剑飞，张冰. 间充质干细胞在癌症治疗中的应用潜能[J]. 医学研究与教育, 2015, 32(5): 93-97.

JU Hailong, LIANG Lu, BIAN Jianfei, ZHANG Bing. Application of potential of mesenchymal stem cell in the treatment of cancer[J]. Medical Reserch and Education, 2015, 32(5): 93-97.

参考文献

[1] BECKER A J, MCCULLOCH E A, TILL J E. Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells[J]. Nature, 1963, 197(2): 452-454.
[2] 瞿海龙, 麻月云, 边剑飞. 干细胞治疗心脏疾患研究进展[J]. 医学研究与教育, 2014, 31(5): 55-58.
[3] 瞿海龙, 边剑飞, 周英莲, 等. 间充质干细胞治疗炎症性心肌病的研究进展[J]. 医学研究与教育, 2012, 29(3): 44-48.
[4] KLINKER M W, WEI C H. Mesenchymal stem cells in the treatment of inflammatory and autoimmune diseases in experimental animal models[J]. World J Stem Cells, 2015, 7(3): 556-567.
[5] LAZARUS H M, HAYNESWORTH S E, GERSON S L. Ex vivo expansion and subsequent infusion of human bone marrow-derived stromal progenitor cells (mesenchymal progenitor cells): implications for therapeutic use[J]. Bone Marrow Transplant, 1995, 16(4): 557-564.
[6] KIM N, CHO S G. New strategies for overcoming limitations of mesenchymal stem cell-based immune modulation[J]. Int J Stem Cells, 2015, 8(1): 54-68.
[7] RAMDASI S, SARANG S, VISWANATHAN C. Potential of Mesenchymal Stem Cell based application in Cancer[J]. Int J Hematol Oncol Stem Cell Res, 2015, 9(2): 95-103.
[8] JEON Y, LEE M S, CHEON Y P. Decreased contact inhibition in mouse adipose mesenchymal stem cells[J]. Balsaenggwa Saengsig, 2012, 16(4): 329-338.
[9] STABILE H, NISTI P, MORRONE S, et al. Multifunctional human CD56 low CD16 low natural killer cells are the prominent subset in bone marrow of both healthy pediatric donors and leukemic patients[J]. Haematologica, 2015, 100(4): 489-498.
[10] MAESTRONI G J, HERTENS E, GALLI P. Factor(s) from nonmacrophage bone marrow stromal cells inhibit Lewis lung carcinoma and B16 melanoma growth in mice[J]. Cell Mol Life Sci, 1999, 55(4): 663-667.
[11] SMITH C L, CHAICHANA K L, LEE Y M, et al. Pre-exposure of human adipose mesenchymal stem cells to soluble factors enhances their homing to brain cancer[J]. Stem Cells Transl Med, 2015, 4(3): 239-251.
[12] SEICEAN A, PETRUSEL L, SEICEAN R. New targeted therapies in pancreatic cancer[J]. World J Gastroenterol, 2015, 21(20): 6127-6145.
[13] FAKIRUDDIN K S, BAHARUDDIN P, LIM M N, et al. Nucleofection optimization and in vitro anti-tumourigenic effect of TRAIL-expressing human adipose-derived mesenchymal stromal cells[J]. Cancer Cell Int, 2014, 14(1): 122.
[14] DWYER R M, KHAN S, BARRY F P, et al. Advances in mesenchymal stem cell-mediated gene therapy for cancer[J]. Stem Cell Res Ther, 2010, 1(3): 25.
[15] LOURENCO S, TEIXEIRA V H, KALBER T, et al. Macrophage migration inhibitory factor-CXCR4 is the dominant chemotactic axis in human mesenchymal stem cell recruitment to tumors[J]. J Immunol, 2015, 194(7): 3463-3474.
[16] GENTSCHEV I, PATIL S S, PETROV I, et al. Oncolytic virotherapy of canine and feline cancer[J]. Viruses, 2014, 6(5): 2122-2137.
[17] YU J M, JUN E S, BAE Y C, et al. Mesenchymal stem cells derived from human adipose tissues favor tumor cell growth in vivo[J]. Stem Cells Dev, 2008, 17(3): 463-473.
[18] GALDERISI U, GIORDANO A, PAGGI M G. The bad and the good of mesenchymal stem cells in cancer: Boosters of tumor growth and vehicles for targeted delivery of anticancer agents[J]. World J Stem Cells, 2010, 2(1): 5-12.
[19] LIS R, TOUBOUL C, MIRSHAHI P, et al. Tumor associated mesenchymal stem cells protects ovarian cancer cells from hyperthermia through CXCL12[J]. Int J Cancer, 2011, 128(3): 715-725.
[20] DJOUAD F1, PLENCE P, BONY C, et al. Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals[J]. Blood, 2003, 102(10): 3837-3844.
[21] MA G, TABANCA N, HUSNU CAN BASER K, et al. Inhibition of NF-kappaB-mediated transcription and induction of apoptosis in human breast cancer cells by epoxypseudoisoeugenol-2-methyl butyrate[J]. Cancer Chemother Pharmacol, 2009, 63(4): 673-680.
[22] DOI C, MAURYA D K, PYLE M M, et al. Cytotherapy with naive rat umbilical cord matrix stem cells significantly attenuates growth of murine pancreatic cancer cells and increases survival in syngeneic mice[J]. Cytotherapy, 2010, 12(3): 408-417.
[23] AKIMOTO K, KIMURA K, NAGANO M, et al. Umbilical cord blood-derived mesenchymal stem cells inhibit, but adipose tissue- derived mesenchymal stem cells promote, glioblastoma multiforme proliferation[J]. Stem Cells Dev, 2013, 22(9): 1370-1386.
[24] WATERMAN R S, HENKLE S L, BETANCOURT A M. Mesenchymal stem cell 1 (MSC1)-based therapy attenuates tumor growth whereas MSC2-treatment promotes tumor growth and metastasis[J]. PLoS One, 2012, 7(9): e45590.