Current Approach to Cancer Stem Cells

Yıl 2022, Cilt: 31 Sayı: 2, 111 - 121, 30.06.2022

Tuğçe Sapmaz Erçakallı , Sait Polat

https://doi.org/10.17827/aktd.1088310

Öz

Cancer Stem Cells (CSC) are cells that are capable of self-renewal and differentiation, such as normal stem cells and are found in many tissues such as breast, brain, lung, prostate, testis, ovary, esophagus, colon, liver. Their origins have not yet been discovered, but a number of hypotheses have been put forward. CSCs are cells that drive tumorigenesis, as well as give rise to a large population of differentiated progeny that make up the bulk of the tumor. Each cancer has biomarkers that identify the stem cell. The same specific signaling pathways play a functional role in CSC renewal and differentiation as with normal stem cells, the only difference being that the same signaling pathways are dysregulated in CSCs.
CSCs play a role in not only the creation of cancer, but also in its evolution, metastasis, and recurrence. MicroRNAs and several signaling pathways such as Wnt/β-catenin, Notch and Hedgehog control the properties of CSCs. CSCs are resistant to conventional chemotherapy and radiation treatment and that CSCs are very likely to be the origin of cancer metastasis. CSCs are believed to be an important target for novel anti-cancer drug discovery. Future studies will lead to the development of therapies that target CSCs for the treatment of cancer.

Anahtar Kelimeler

metastasis., Cancer stem cell, cancer stem cell markers, normal stem cell, metastasis.

Kanser Kök Hücrelerine Güncel Yaklaşım

Öz

Kanser Kök Hücreleri (KaKH), normal kök hücreler gibi kendi kendini yenileme ve farklılaşma yeteneğine sahip hücreler olup meme, beyin, akciğer, prostat, testis, over, yemek borusu, kolon, karaciğer gibi birçok dokuda bulunur. Kökenleri henüz keşfedilmemiştir, ancak bu konuda bir dizi hipotez öne sürülmüştür. KaKH tümörün başlangıcından sorumlu ve tümör dokusundaki çok sayıda farklılaşmış hücre topluluğunu oluşturan hücrelerdir. Her bir kanserin kök hücresini tanımlayan biyobelirteçler vardır. KaKH’lerin ve normal kök hücrelerin kendi kendini yenileme ve farklılaşmasında aynı özgü sinyal iletim sistemleri rol oynamaktadır. Fakat KaKH’lerde bu sinyal iletim sistemlerinin düzenlenmesi değişmektedir.
KaKH'leri sadece kanserin yaratılmasında değil, evriminde, metastazında ve geç dönemde yeniden ortaya çıkmasında da rol oynamaktadır. MikroRNA'lar, Wnt/β-catenin, Notch ve Hedgehog gibi sinyal yolaklarından oluşan bir düzenleme ağı KaKH özelliklerini kontrol eder. KaKH'leri kanser tedavisinde, konvansiyonel kemoterapi ve radyasyon tedavisine karşı dirençte rol oynarak, kanser metastazının kökeni olarak değerlendirilebilir. KaKH'leri yeni kanser önleyici ilaç keşfi için tedavi protokollerinde hedef haline gelmiştir. Gelecekteki çalışmalar kanserin tedavisi için KaKH’leri hedef alan tedavilerin geliştirilmesine öncülük edecektir.

Anahtar Kelimeler

Kanser Kök Hücresi, Kanser kök hücresi belirteçleri, Normal kök hücre, Metastaz

Kaynakça

• 1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4. PMID: 33538338.
• 2. Can A. KÖK HÜCRE: Biyolojisi, Türleri ve Tedavide Kullanımları. Ankara, 2014; 603-625.
• 3. Li L, Neaves WB. Normal stem cells and cancer stem cells: the niche matters. Cancer Res. 2006; May 1 66(9):4553-7.
• 4. Yang YM, Chang JW. Current status and issues in cancer stem cell study. Cancer Invest. 2008; 26:741-755.
• 5. Pham PV. Breast Cancer Stem Cells & Therapy Resistance. SpringerBriefs in Stem Cells. 2015; DOI 10.1007/978-3-319-22020-8_2.
• 6. Atena M, Reza AM, Mehran G. A Review on the Biology of Cancer Stem Cells. Stem Cell Discovery. 2014; 4,83-89.
• 7. Tuna M. Solid tümörlerde ve lösemilerde kanser kök hücreleri. Türk Onkoloji Dergisi. 2009; 24(1):42-47.
• 8. Yu Z, Pestell TG, Lisanti MP, Pestell RG. Cancer Stem Cells. Int J Biochem Cell Biol. 2012; December 44(12): 2144–2151.
• 9. Aguirre-Ghiso JA. Models, mechanisms and clinical evidence for cancer dormancy. Nat Rev Cancer. 2007; 7:834-846.
• 10. Al-Hajj M, Clarke MF. Self-renewal and solid tumor stem cells. Oncogene. 2004; 23(43):7274-82.
• 11. Zhou HM, Zhang JG, Zhang X, Li Q. Targeting cancer stem cells for reversing therapy resistance: mechanism, signaling, and prospective agents. Signal Transduct Target Ther. 2021 Feb 15;6(1):62. doi: 10.1038/s41392-020-00430-1. PMID: 33589595; PMCID: PMC7884707.
• 12. Singh, S. K. et al. Identification of human brain tumour initiating cells. Nature.2004; 432, 396–401.
• 13. Ma, S. et al. Identification and characterization of tumorigenic liver cancer stem/progenitor cells. Gastroenterology. 2007; 132, 2542–2556.
• 14. 14. Beier, D. et al. CD133(+) and CD133(-) glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles. Cancer Res. 2007; 67, 4010–4015.
• 15. Ricci-Vitiani, L. et al. Identification and expansion of human colon-cancer-initiating cells. Nature. 2007; 445, 111–115.
• 16. Baba, T. et al. Epigenetic regulation of CD133 and tumorigenicity of CD133+ ovarian cancer cells. Oncogene. 2009; 28, 209–218.
• 17. Haraguchi, N. et al. CD133+CD44+ population efficiently enriches colon cancer initiating cells. Ann. Surg. Oncol. 2008; 15, 2927–2933.
• 18. Silva, I. A. et al. Aldehyde dehydrogenase in combination with CD133 defines angiogenic ovarian cancer stem cells that portend poor patient survival. Cancer Res. 2011; 71, 3991–4001.
• 19. Dalerba, P. et al. Phenotypic characterization of human colorectal cancer stem cells. Proc. Natl Acad. Sci. USA. 2007; 104, 10158–10163.
• 20. Du, L. et al. CD44 is of functional importance for colorectal cancer stem cells. Clin. Cancer Res. : Off. J. Am. Assoc. Cancer Res. 2008; 14, 6751–6760.
• 21. Lee, C. J., Dosch, J. & Simeone, D. M. Pancreatic cancer stem cells. J. Clin. Oncol. 2008; 26, 2806–2812.
• 22. Alvero, A. B. et al. Molecular phenotyping of human ovarian cancer stem cells unravels the mechanisms for repair and chemoresistance. Cell Cycle. 2009; 8, 158–166.
• 23. Takaishi, S. et al. Identification of gastric cancer stem cells using the cell surface marker CD44. Stem Cells (Dayt., Ohio). 2009; 27, 1006–1020.
• 24. Al-Hajj, M. et al. Prospective identification of tumorigenic breast cancer cells. Proc. Natl Acad. Sci. USA. 2003; 100, 3983–3988.
• 25. Shmelkov, S. V. et al. CD133 expression is not restricted to stem cells, and both CD133+ and CD133- metastatic colon cancer cells initiate tumors. J. Clin. Invest. 2008; 118, 2111–2120.
• 26. Yamashita, T. et al. EpCAM-positive hepatocellular carcinoma cells are tumorinitiating cells with stem/progenitor cell features. Gastroenterology. 2009; 136, 1012–1024.
• 27. Yang, Z. F. et al. Significance of CD90+ cancer stem cells in human liver cancer. Cancer Cell. 2008; 13, 153–166.
• 28. True, L. D. et al. CD90/THY1 is overexpressed in prostate cancer-associated fibroblasts and could serve as a cancer biomarker. Mod. Pathol. 2010; 23, 1346–1356.
• 29. Buishand, F. O. et al. Identification of CD90 as putative cancer stem cell marker and therapeutic target in insulinomas. Stem Cells Dev. 2016; 25, 826–835.
• 30. Chen, W.-C. et al. Cancer stem cell marker CD90 inhibits ovarian cancer formation via β3 integrin. Int. J. Oncol. 2016; 49, 1881–1889.
• 31. Allan AL, Vantyghem SA, Tuck AB, Chambers AF. Tumor dormancy and cancer stem cells: implications for the biology and treatment of breast cancer metastasis. Breast Dis, 2006; 26: 87-98.
• 32. Hope KJ, Jin L, Dick JE. Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nat Immunol, 2004; 5: 738-743.
• 33. Kucia M, Ratajczak MZ. Stem cells as a two edged sword from degeneration to humor formation. J Physiol Pharmacol, 2006; 57 Supply 7: 5-16.
• 34. Li F, Tiede B, Massague J, Kang Y. Beyond tumorigenesis: cancer stem cells in metastasis. Cell Res, 2007; 17:3-14.
• 35. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA. Induced pluripotent stem cell lines derived from human somatic cells. Science, 2007; Dec 21;318(5858):1917-20
• 36. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 2007; Nov 30 131(5):861-72.
• 37. Takebe N, Ivy SP. Controversies in cancer stem cells: targeting embryonic signaling pathways. Clin Cancer Res, 2010; Jun 15 16(12):3106-12.
• 38. Hobmayer B, Rentzsch F, Kuhn K, Happel CM, von Laue CC, Snyder P, Rothbächer U, Holstein TW. WNT signalling molecules act in axis formation in the diploblastic metazoan Hydra. Nature, 2000; Sep 14 407(6801):186-9.
• 39. Li Y, Lu W, King TD, Liu CC, Bijur GN, Bu G. Dkk1 stabilizes Wnt co-receptor LRP6: implication for Wnt ligand-induced LRP6 down-regulation. PLoS One, 2010; Jun 8 5(6):e11014.
• 40. Sparks AB, Morin PJ, Vogelstein B, Kinzler KW. Mutational analysis of the APC/beta-catenin/Tcf pathway in colorectal cancer. Cancer Res., 1998; Mar 15 58(6):1130-4.
• 41. Naka K, Hoshii T, Hirao A. Novel therapeutic approach to eradicate tyrosine kinase inhibitor resistant chronic myeloid leukemia stem cells. Cancer Sci, 2010; Jul 101(7):1577-81.
• 42. Mueller MT, Hermann PC, Witthauer J, Rubio-Viqueira B, Leicht SF, Huber S, Ellwart JW, Mustafa M, Bartenstein P, D'Haese JG, Schoenberg MH, Berger F, Jauch KW, Hidalgo M, Heeschen C. Combined targeted treatment to eliminate tumorigenic cancer stem cells in human pancreatic cancer. Gastroenterology, 2009; Sep 137(3):1102-13.
• 43. Morrison SJ, Perez SE, Qiao Z, Verdi JM, Hicks C, Weinmaster G, Anderson DJ. Transient Notch activation initiates an irreversible switch from neurogenesis to gliogenesis by neural crest stem cells. Cell, 2000; May 26 101(5):499-510.
• 44. Hoey T, Yen WC, Axelrod F, Basi J, Donigian L, Dylla S, Fitch-Bruhns M, Lazetic S, Park IK, Sato A, Satyal S, Wang X, Clarke MF, Lewicki J, Gurney A. DLL4 blockade inhibits tumor growth and reduces tumor-initiating cell frequency. Cell Stem Cell, 2009; Aug 7 5(2):168-77.
• 45. Hill R, Wu H. PTEN, stem cells, and cancer stem cells. J Biol Chem., 2009; May 1 284(18):11755-9.
• 46. Hambardzumyan D, Becher OJ, Rosenblum MK, Pandolfi PP, Manova-Todorova K, Holland EC. PI3K pathway regulates survival of cancer stem cells residing in the perivascular niche following radiation in medulloblastoma in vivo. Genes Dev, 2008; Feb 15 22(4):436-48.
• 47. Lin L, Liu Y, Li H, Li PK, Fuchs J, Shibata H, Iwabuchi Y, Lin J. Targeting colon cancer stem cells using a new curcumin analogue, GO-Y030. Br J Cancer, 2011; Jul 12 105(2):212-20.
• 48. Lonardo E, Hermann PC, Mueller MT, Huber S, Balic A, Miranda-Lorenzo I, Zagorac S, Alcala S, Rodriguez-Arabaolaza I, Ramirez JC, Torres-Ruíz R, Garcia E, Hidalgo M, Cebrián DÁ, Heuchel R, Löhr M, Berger F, Bartenstein P, Aicher A, Heeschen C. Nodal/Activin signaling drives self-renewal and tumorigenicity of pancreatic cancer stem cells and provides a target for combined drug therapy. Cell Stem Cell, 2011; Nov 4 9(5):433-46.
• 49. Altınok B, Sunguroğlu A. WNT Sinyal Yolağı ve Kanser. Ankara Sağlık Hizmetleri, Dergisi. 2016; Cilt 15, Sayı 2.
• 50. Browner WS, Kahn AJ, Ziv E, Reiner AP, Oshima J, Cawthon RM, Hsueh WC, Cummings SR. The genetics of human longevity. Am J Med., 2004; Dec 1 117(11):851-60.
• 51. Bakkenist CJ, Kastan MB. DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature, 2003; Jan 30:421(6922):499-506.
• 52. Manabu T, Fumitaka K, Soichiro Y, Satoru K, Yasuhisa F, Len N. Potential role of Hsp90 inhibitors in overcoming cisplatin resistance of bladder cancer-initiating cells, International Journal of Cancer, 2012; 131:987-996.
• 53. Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M. ALDH is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell, 2007; 1:555-567.
• 54. Agarwal S, Hartz AM, Elmquist WF, Bauer B. Breast cancer resistance protein and P-glycoprotein in brain cancer: two gatekeepers team up. Curr Pharm Des., 2011; 17(26):2793-802.
• 55. Kanwar SS, Yu Y, Nautiyal J, Patel BB, Padhye S, Sarkar FH, Majumdar AP. Difluorinated-curcumin (CDF): a novel curcumin analog is a potent inhibitor of colon cancer stem-like cells. Pharm Res., 2011; Apr 28(4):827-38.
• 56. Labayle D, Fischer D, Vielh P, Drouhin F, Pariente A, Bories C, Duhamel O, Trousset M, Attali P. Sulindac causes regression of rectal polyps in familial adenomatous polyposis. Gastroenterology.,1991; Sep 101(3):635-9.
• 57. Akhter J, Chen X, Bowrey P, Bolton EJ, Morris DL. Vitamin D3 analog, EB1089, inhibits growth of subcutaneous xenografts of the human colon cancer cell line, LoVo, in a nude mouse model. Dis Colon Rectum.,1997; Mar 40(3):317-21.
• 58. Ettenberg SA1, Charlat O, Daley MP, Liu S, Vincent KJ, Stuart DD, Schuller AG, Yuan J, Ospina B, Green J, Yu Q, Walsh R, Li S, Schmitz R, Heine H, Bilic S, Ostrom L, Mosher R, Hartlepp KF, Zhu Z, Fawell S, Yao YM, Stover D, Finan PM, Porter JA, Sellers WR, Klagge IM, Cong F. Inhibition of tumorigenesis driven by different Wnt proteins requires blockade of distinct ligand-binding regions by LRP6 antibodies. Proc Natl Acad Sci U S A., 2010; Aug 31 107(35):15473-8.
• 59. Krause M, Yaromina A, Eicheler W, Koch U, Baumann M. Cancer stem cells: targets and potential biomarkers for radiotherapy. Clin Cancer Res., 2011; Dec 1 17(23):7224-9.
• 60. Baschnagel A, Russo A, Burgan WE, Carter D, Beam K, Palmieri D, Steeg PS, Tofilon P, Camphausen K. Vorinostat enhances the radiosensitivity of a breast cancer brain metastatic cell line grown in vitro and as intracranial xenografts. Mol Cancer Ther., 2009; Jun 8(6):1589-95.
• 61. Scheel C, Weinberg RA. Phenotypic plasticity and epithelial-mesenchymal transitions in cancer and normal stem cells?. Int J Cancer., 2011; Nov 15 129(10):2310-4.
• 62. Gumireddy K, Li A, Gimotty PA, Klein-Szanto AJ, Showe LC, Katsaros D, Coukos G, Zhang L, Huang Q. KLF17 is a negative regulator of epithelial-mesenchymal transition and metastasis in breast cancer. Nat Cell Biol., 2009; Nov 11(11):1297-304.
• 63. Ma I, Allan AL. The role of human aldehyde dehydrogenase in normal and cancer stem cells. Stem Cell Rev., 2011; Jun 7(2):292-306.
• 64. Islam SS, Al-Sharif I, Sultan A, Al-Mazrou A, Remmal A, Aboussekhra A. Eugenol potentiates cisplatin anti-cancer activity through inhibition of ALDH-positive breast cancer stem cells and the NF-κB signaling pathway. Mol Carcinog. 2018 Mar;57(3):333-346.
• 65. Yang YP, Chien Y, Chiou GY, Cherng JY, Wang ML, Lo WL, Chang YL, Huang PI, Chen YW, Shih YH, Chen MT, Chiou SH. Inhibition of cancer stem cell-like properties and reduced chemoradioresistance of glioblastoma using microRNA145 with cationic polyurethane-short branch PEI. Biomaterials, 2012; Feb 33(5):1462-76.
• 66. Liu C, Tang DG. MicroRNA regulation of cancer stem cells. Cancer Res., 2011; Sep 15 71(18):5950-4.
• 67. Garofalo M, Croce CM. Role of microRNAs in maintaining cancer stem cells. Adv Drug Deliv Rev. 2015 Jan;81:53-61.