High Capacity of the Metastatic Breast Tumor Cells inSphere Formation: Clue for Chemoresistance in Triple-Negative Breast Cancer

High Capacity of the Metastatic Breast Tumor Cells inSphere Formation: Clue for Chemoresistance in Triple-Negative Breast Cancer

Metastasis is a major cause of cancer-related death in Triple-Negative Breast Cancer (TNBC). In TNBC, there is a significant correlation between metastasis and chemoresistance. Cancer relapse and metastasis are associated with the part of cancer cells with stem cell properties. These cancer stem cells are resistant to current cancer treatments. Due to their resistant nature, a significant relationship exists between the amount of cancer stem cells and chemoresistance. To our knowledge, to date, no comparative study was conducted on the number of these cells in metastatic loci vs. primary tumor site. METHODSIn the present study, after developing a metastatic animal model of TNBC, metastatic and primary tumor cells were extracted from the lung and primary tumor of cancerous mice, respectively. In the next step, the sphere formation ability as a reliable in vitro assay to assess the presence and self-renewal ability of CSCs, in metastatic and primary tumor cells was evaluated separately.RESULTSThe results showed that sphere formation ability, and consequently the population of cancer stem cells among metastatic tumor cells was significantly higher.CONCLUSIONA higher percent of CSCs in lung metastatic site, compared with the primary tumor site, can partly explain the reasons for the chemoresistance and relapse in metastatic TNBC.

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  • 1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016;66(1):7–30.
  • 2. Yao H, He G, Yan S, Chen C, Song L, Rosol TJ, et al. Triple-negative breast cancer: is there a treatment on the horizon? Oncotarget 2017;8(1):1913–24.
  • 3. Isakoff SJ. Triple-negative breast cancer: role of specific chemotherapy agents. Cancer J 2010;16(1):53–61.
  • 4. Acharyya S, Oskarsson T, Vanharanta S, Malladi S, Kim J, Morris PG, et al. A CXCL1 paracrine network links cancer chemoresistance and metastasis. Cell 2012;150(1):165–78.
  • 5. Gonzalez-Angulo AM, Morales-Vasquez F, Hortobagyi GN. Overview of resistance to systemic therapy in patients with breast cancer. Adv Exp Med Biol 2007;608:1–22.
  • 6. Piccart MJ, Wood WC, Hung CM, Solin LJ, Cardoso F. Breast Cancer Management and Molecular Medicine. Springer Science & Business Media; 2007.
  • 7. Lujambio A, Calin GA, Villanueva A, Ropero S, Sánchez-Céspedes M, Blanco D, et al. A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci U S A 2008;105(36):13556–61.
  • 8. Ventura A, Jacks T. MicroRNAs and cancer: short RNAs go a long way. Cell 2009;136(4):586–91.
  • 9. Cameron MD, Schmidt EE, Kerkvliet N, Nadkarni KV, Morris VL, Groom AC, et al. Temporal progression of metastasis in lung: cell survival, dormancy, and location dependence of metastatic inefficiency. Cancer Res 2000;60(9):2541–6.
  • 10.Borah A, Raveendran S, Rochani A, Maekawa T, Kumar DS. Targeting self-renewal pathways in cancer stem cells: clinical implications for cancer therapy. Oncogenesis 2015;4(11):177.
  • 11. Lin Y, Zhong Y, Guan H, Zhang X, Sun Q. CD44+/ CD24- phenotype contributes to malignant relapse following surgical resection and chemotherapy in patients with invasive ductal carcinoma. J Exp Clin Cancer Res 2012;31(1):59.
  • 12.Fillmore CM, Kuperwasser C. Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy. Breast Cancer Res 2008;10(2):R25.
  • 13.Morrison BJ, Steel JC, Morris JC. Sphere culture of murine lung cancer cell lines are enriched with cancer initiating cells. PLoS One 2012;7(11):49752.
  • 14.Amaral RLF, Miranda M, Marcato PD, Swiech K. Comparative Analysis of 3D Bladder Tumor Spheroids Obtained by Forced Floating and Hanging Drop Methods for Drug Screening. Front Physiol 2017;8:605.
  • 15.Velasco-Velázquez MA, Popov VM, Lisanti MP, Pestell RG. The role of breast cancer stem cells in metastasis and therapeutic implications. Am J Pathol 2011;179(1):2–11.
  • 16.Kamalabadi-Farahani M, H Najafabadi MR, Jabbarpour Z. Apoptotic Resistance of Metastatic Tumor Cells in Triple Negative Breast Cancer: Roles of Death Receptor-5. Asian Pac J Cancer Prev 2019;20(6):1743–48.
  • 17.Haffty BG, Yang Q, Reiss M, Kearney T, Higgins SA, Weidhaas J, et al. Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer. J Clin Oncol 2006;24(36):5652–7.
  • 18.Rivera E, Gomez H. Chemotherapy resistance in metastatic breast cancer: the evolving role of ixabepilone. Breast Cancer Res 2010;12 Suppl 2(Suppl 2):S2.
  • 19.Davuluri G, Schiemann WP, Plow EF, Sossey-Alaoui K. Loss of WAVE3 sensitizes triple-negative breast cancers to chemotherapeutics by inhibiting the STAT-HIF-1α-mediated angiogenesis. JAKSTAT 2015;3(4):e1009276.
  • 20.O’Brien CA, Kreso A, Jamieson CH. Cancer stem cells and self-renewal. Clin Cancer Res 2010;16(12):3113–20.
  • 21.Grimshaw MJ, Cooper L, Papazisis K, Coleman JA, Bohnenkamp HR, Chiapero-Stanke L, et al. Mammosphere culture of metastatic breast cancer cells enriches for tumorigenic breast cancer cells. Breast Cancer Res 2008;10(3):R52.
  • 22.Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A 2003;100(7):3983–8.
  • 23.Shackleton M, Quintana E, Fearon ER, Morrison SJ. Heterogeneity in cancer: cancer stem cells versus clonal evolution. Cell 2009;138(5):822–9.
  • 24.Clayton H, Titley I, Vivanco Md. Growth and differentiation of progenitor/stem cells derived from the human mammary gland. Exp Cell Res 2004;297(2):444–60.
  • 25.Alvi AJ, Clayton H, Joshi C, Enver T, Ashworth A, Vivanco Md, et al. Functional and molecular characterisation of mammary side population cells. Breast Cancer Res 2003;5(1):R1–8.
  • 26.Liu BY, McDermott SP, Khwaja SS, Alexander CM. The transforming activity of Wnt effectors correlates with their ability to induce the accumulation of mammary progenitor cells. Proc Natl Acad Sci U S A 2004;101(12):4158–63.
  • 27.Britton KM, Kirby JA, Lennard TW, Meeson AP. Cancer stem cells and side population cells in breast cancer and metastasis. Cancers (Basel) 2011;3(2):2106–30.
Türk Onkoloji Dergisi-Cover
  • ISSN: 1300-7467
  • Başlangıç: 2015
  • Yayıncı: Ali Cangül
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