Mezenkimal Kök Hücrelerin Meme Kanseri Tedavisinde Güncel Katkıları
Mezenkimal kök hücreler (MKH) erişkin dokulardan elde edilen pluripotent kök hücrelerdir.Mezenki-mal kök hücrelerin plastisite, farklılaşabilme, immünmodülatör aktiviteleri onları dokurejenerasyonu, hedefli ilaç taşıma, yara iyileşmesi ve kanser gibi birçok alanda araştırılmayasevketmiştir. MKH’lerin, yarada olduğu gibi salgıladıkları enflamatuar ve sitokin benzerliklerisebebiyle kanserde de tümörlü ve metastatik bölgeye migrasyonu ve tropizmi olduğu bilinmektedir.Ancak literatürde MKH’lerin tümörogenezi arttırdığına veya azalttığına dair çelişen bilgilermevcuttur. MKH’lerin immünmodülatör özel-likleri ile kanser hücrelerine karşı immün baskılayıcıolabildikleri gibi immün arttırıcı da olabildikleri bilinmektedir. Meme kanserinde MKH’lerin terapötikpotansiyeli ise birçok kaynak tarafından destek-lenmektedir. Biz bu eleştiri yazımızda mezenkimalkök hücrelerin meme kanseri progresyonu üzerinde etkilerini ve tedavi mekanizmalarını güncel bilgiile özetleyeceğiz.
Mezenkimal Kök Hücrelerin Meme Kanseri Tedavisinde Güncel Katkıları
Mesenchymal stem cells (MSCs) are pluripotent stem cells derived from adult tissues. The plasticityof mesenchymal stem cells, differentiation, immunomodulatory activities have led them toinvestigate in many areas such as tissue regeneration, target drug delivery, wound healing andcancer. MSCs migrate to the region and have tropic and penetrate the tumor and metastatic regionsto remove the bladder. However, in the literature there is information on the extent to which MSCsincrease or decrease tumorigenesis. It is known that MSCs can be immunosuppressants againstcancer cells as well as immunostimulants with their immunomodulatory properties. The therapeuticpotential of MDRs in breast cancer is supported by a wide variety of sources. We will summarize theinteraction and treatment mechanisms of mesenchymal stem cells on breast cancer progression withcurrent knowledge.
___
- 1. Dominici M, Le Blanc K, Mueller I, Sla-per-
Cortenbach I, Marini F, Krause D, Deans R,
Keating A, Prockop D, Horwitz E. Minimal
criteria for defining multipotent mesenchymal
stromal cells. The International
Society for Cellular Therapy position statement.
Cytotherapy 2006; 8: 315-317.
2. Barzilay R, Melamed E, Offen D. Introducing
transcription factors to multipotent
mesenchymal stem cells: making transdifferentiation
possible. Stem Cells 2009; 27:
2509- 2515.
3. Lindner U, Kramer J, Rohwedel J, Schlenke
P. Mesenchymal Stem or Stromal Cells:
Toward a Better Understanding of Their
Biology?. Transfus Med Hemother 2010; 37,
75-78.
4. Di Nicola M, Carlo-Stella C, Magni M, Milanesi
M, Longoni PD, et al. Human bone marrow
stromal cells suppress T-lymphocyte proliferation
induced by cellular or nonspecific mitogenic
stimuli. Blood 2002; 99: 3838-3843.
5. Raffaghello L, Bianchi G, Bertolotto M, Montecucco
F, Busca A, et al. Human mesenchymal
stem cells inhibit neutrophil apoptosis:
a model for neutrophil preservation in the
bone marrow niche. Stem Cells 2008; 26:
151-162.
6. Aggarwal S, Pittenger MF, Human mesenchymal
stem cells modulate allogeneic immune
cell responses. Blood 105: 1815-1822,
(2005).
7. Trim N, Morgan S, Evans M, Issa R, Fine D, et
al. Hepatic stellate cells express the low
affinity nerve growth factor receptor p75
and undergo apoptosis in response to nerve
growth factor stimulation. Am J Pathol
2000; 156: 1235-1243.
8. Meisel R, Zibert A, Laryea M, Göbel U, Däubener
W, et al. Human bone marrow stromal
cells inhibit allogeneic T-cell responses by
indoleamine 2,3-dioxygenase-mediated tryptophan
degradation. Blood 2004; 103:
4619-4621.
9. Klopp A H, Gupta A, Spaeth E, Andreeff M. &
Marini F., 3rd., Dissecting a discrepancy in
the literature: do mesenchymal stem cel-ls
support or suppress tumor growth? Stem
Cells, Vol.29, No.1, pp. 11-19, (2011).
10. Krabbe C.; Zimmer J. & Meyer M., Neural
transdifferentiation of mesenchymal stem
cells--a critical review. Apmis, Vol.113,
No.11-12, pp. 831-844, (2005).
11. Patel S. A.; Heinrich A. C.; Reddy B. Y.; Srinivas
B.; Heidaran N. & Rameshwar P., Breast
cancer biology: the multifaceted roles of mesenchymal
stem cells. J Oncol, Vol.2008, pp.
425895, (2008).
12. Uccelli A.; Moretta L. & Pistoia V., Mesenchymal
stem cells in health and disease. Nat Rev
Immunol, Vol.8, No.9, pp. 726-736, (2008).
13. Beckermann B.M., Kallifatidis G., Groth A.,
Frommhold D., Apel A., Mattern J., Salnikov
A.V., Moldenhauer G., Wagner W., Diehlmann
A., et al. VEGF expression by mesenchymal
stem cells contributes to angiogenesis in
pancreatic carcinoma. Br J Cancer 2008; 99:
622-631.
14. Block GJ, Ohkouchi S, Fung F, Frenkel J,
Gregory C, Pochampally R, DiMattia G, Sullivan
DE, Prockop DJ. Multipotent stromal
cells are activated to reduce apoptosis in
part by upregulation and secretion of stanniocalcin-
1. Stem Cells 2009; 27: 670–681.
15. Zhang Y, Daquinag A, Traktuev DO, Ama-ya-
Manzanares F, Simmons PJ, March KL,
Pasqualini R, Arap W, Kolonin MG. White
adipose tissue cells are recruited by experimental
tumors and promote cancer progression
in mouse models. Cancer Res 2009; 69:
5259-5266.
16. Jotzu C, Alt E, Welte G, Li J, Hennessy BT,
Devarajan E, Krishnappa S, Pinilla S, Droll L,
Song YH. Adipose tissue derived stem cells
differentiate into carcinoma-associated
fibroblast-like cells under the influence of
tumor derived factors. Cell Oncol 2011; 34:
55-67.
17. Pinilla S, Alt E, Abdul Khalek FJ, Jotzu C,
Muehlberg F, Beckmann C, Song YH. Tissue
resident stem cells produce CCL5 under the
influence of cancer cells and thereby promote
breast cancer cell invasion. Cancer Lett
2009; 284: 80-85.
18. Krohn A, Song YH, Muehlberg F, Droll L,
Beckmann C, Alt E. CXCR4 receptor positive
spheroid forming cells are responsible for
tumor invasion in vitro. Cancer Lett 2009;
280: 65-71.
19. Khakoo AY, Pati S, Anderson SA, Reid W,
Elshal MF, Rovira II, Nguyen AT, Malide D,
Combs CA, Hall G, et al. Human mesenchymal
stem cells exert potent antitumorigenic
effects in a model of Kaposi’s sarcoma. J
Exp Med 2006; 203:1235-1247.
20. Qiao L, Xu Z, Zhao T, Zhao Z, Shi M, Zhao RC,
Ye L, Zhang X. Suppression of tumorigenesis
by human mesenchymal stem cells
in a hepatoma model. Cell Res 2008; 18:
500-507.
21. Qiao L, Xu ZL, Zhao TJ, Ye LH, Zhang XD.
Dkk-1 secreted by mesenchymal stem cells
inhibits growth of breast cancer cells via
depression of Wnt signalling. Cancer Lett
2008; 269: 67-77.
22. Zhu Y, Sun Z, Han Q, Liao L, Wang J, Bian C,
Li J, Yan X, Liu Y, Shao C, et al. Human
mesenchymal stem cells inhibit cancer cell
proliferation by secreting DKK-1. Leukemia
2009; 23: 925-933.
23. Cousin B, Ravet E, Poglio S, de Toni F, Bertuzzi
M, Lulka H, Touil I, Andre M, Grolleau
JL, Peron JM, et al. Adult stromal cells
derived from human adipose tissue provoke
pancreatic cancer cell death both in vitro and
in vivo. PLoS ONE 2009; 4(7): e6278.
24. Dasari VR, Velpula KK, Kaur K, Fassett D,
Klopfenstein JD, Dinh DH, Gujrati M, Rao JS.
Cord blood stem cell-mediated induction of
apoptosis in glioma downregulates X-linked
inhibitor of apoptosis protein (XIAP) PLoS
ONE 2010; 5(7): e11813.
25. Otsu K, Das S, Houser SD, Quadri SK,
Bhattacharya S, Bhattacharya J. Concentration-
dependent inhibition of angiogenesis by
mesenchymal stem cells. Blood 2009; 113:
4197-4205.
26. Li Z,, Fan D, Xiong D, Mesenchymal stem
cells as delivery vectors for anti-tumor therapy,
Stem Cell Investigation 2015.
27. Parkin DM, Bray F, Ferlay J, Pisani P. Estimating
the world cancer burden: Globocan 2000.
Int J Cancer 2001; 94: 153-156.
28. Roukos DH, Murray S, Briasoulis E. Molecular
genetic tools shape a roadmap towards
a more accurate prognostic prediction and
personalized management of cancer. Cancer
BiolTher 2007; 6: 308-312.
29. Lehmann BD, Bauer JA, Chen X, Sanders
ME, Chakravarthy AB, Shyr Y, Pietenpol JA.
Identification of human triplenegative breast
cancer subtypes and preclinical models for
selection of targeted therapies. J Clin Invest
2011; 121: 2750-2767.
30. Ryu H, Oh JE, Rhee KJ, Baik SK, Kim J, Kang
SJ, Sohn JH, Choi E, Shin HC, Kim YM, Kim
HS, Bae KS, Eom YW. Adipose tissue-derived
mesenchymal stem cells cultured at high
density express IFN-beta and suppress the
growth of MCF-7 human breast cancer cells.
Cancer Lett 2014; 352: 220-227.
31. Zhou Y, Zuo D, Wang M, Zhang Y, Yu M, Yang
J, Yao Z. Effect of truncated neurokinin-1 receptor
expression changes on the interaction
between human breast cancer and bone marrow-
derived mesenchymal stem cells. Genes
Cells 2014;19: 676-691.
32. Kucerova L, Skolekova S, Matuskova M,
Bohac M, Kozovska Z. Altered features and
increased chemosensitivity of human breast
cancer cells mediated by adipose tissue-derived
mesenchymal stromal cells. BMC Cancer
2013; 13: 535.
33. Leng L, Wang Y, He N, Wang D, Zhao Q, Feng
G, Su W, Xu Y, Han Z, Kong D, Cheng Z, Xiang
R, Li Z. Molecular imaging for assessment of
mesenchymal stem cells mediated breast
cancer therapy. Biomaterials 2014; 35:
5162-5170.
34. Vegh I, Grau M, Gracia M, Grande J, de la Torre
P, Flores AI. Decidua mesenchymal stem
cells migrated toward mammary tumors in
vitro and in vivo affecting tumor growth and
tumor development. Cancer Gene Ther 2013;
20: 8-16.
35. Dwyer RM, Potter-Beirne SM, Harrington KA,
Lowery AJ, Hennessy E, Murphy JM et al.
Monocyte chemotactic protein-1 secreted by
primary breast tumors stimulates migration
of mesenchymal stem cells. Clin Cancer Res
2007; 13(17): 5020-5027.
36. Lin SY, Yang J, Everett AD, Clevenger
CV, Koneru M, Mishra PJ, Kamen B,
Banerjee D, Glod J. The isolation of novel
mesenchymal stromal cell chemotactic
factors from the conditioned medium of
tumor cells. Exp Cell Res 2008; 314(17):
3107-3117.
37. Gutova M, Najbauer J, Frank RT, Kendall
SE, Gevorgyan A, Metz MZ, et al. Urokinase
plasminogen activator and urokinase plasminogen
activator receptor mediate human
stem cell tropism to malignant solid tumors.
Stem Cells 2008; 26(6): 1406-1413.
38. Pulukuri SMK, Gorantla B, Dasari VR, Gondi
CS, Rao JS. Epigenetic upregulation of urokinase
plasminogen activator promotes the
tropism of mesenchymal stem cells for
tumor cells. Mol Cancer Res 2010; 8(8):
1074-1083.
39. Ritter E, Perry A, Yu J, Wang T, Tang L, Bieberich
E. Breast cancer cell-derived fibroblast
growth factor 2 and vascular endothelial
growth factor are chemoattractants for
bone marrow stromal stem cells. Ann Surg
2008; 247(2): 310-314.
40. Rattigan Y, Hsu J-M, Mishra PJ, Glod J, Banerjee
D. Interleukin 6 mediated recruitment
of mesenchymal stem cells to the hypoxic
tumor milieu. Exp Cell Res 2010; 316(20):
3417-3124.
41. Shah K. Mesenchymal stem cells engineered
for cancer therapy. Adv Drug Deliv Rev 2012;
64: 739-748.
42. Studeny M, Marini FC, Champlin RE, Zompetta
C, Fidler IJ, Andreeff M. Bone marrow-derived
mesenchymal stem cells as vehicles for
interferon-beta delivery into tumors. Cancer
Res 2002; 62(13): 3603-3608.
43. Studeny M, Marini FC, Dembinski JL, Zompetta
C, Cabreira-Hansen M, Bekele BN, et al.
Mesenchymal stem cells: potential precursors
for tumor stroma and targeted-delivery
vehicles for anticancer agents. J Natl Cancer
Inst 2004; 96(21): 1593-1603.
44. Stoff-Khalili MA, Rivera AA, Mathis JM, Banerjee
NS, Moon AS, Hess A, et al. Mesenchymal
stem cells as a vehicle for targeted
delivery of CRAds to lung metastases of
breast carcinoma. Breast Cancer Res Treat
2007; 05(2):157-167.
45. Leng L, Wang Y, He N, Wang D, Zhao Q, Feng
G, Su W, Xu Y, Han Z, Kong D, Cheng Z, Xiang
R, Li Z. Molecular imaging for assessment of
mesenchymal stem cells mediated breast
cancer therapy. Biomaterials 2014; 35:
5162-5170.
46. Gjorgieva D, Zaidman N, Bosnakovski D.
Mesenchymal stem cells for anti-cancer drug
delivery. Rec Pat Anticancer Drug Discov
2013; 8, 310-318.
47. Griffin MD, Elliman SJ, Cahill E, English K,
Ceredig R, Ritter T. Concise review: adult
mesenchymal stromal cell therapy for inflammatory
diseases: how well are we joining
the dots?. Stem Cells 2013; 31: 2033-2041.
48. Stark GR, Kerr IM, Williams BR, Silverman
RH, Schreiber RD. How cells respond to interferons.
Annual Review of Biochemistry
1998; 67: 227-264.
49. Celada A, Schreiber RD. Role of protein kinase
C and intracellular calcium mobilization in
the induction of macrophage tumoricidal activity
by interferon-gamma. Journal of Immunology
1986; 137: 2373-2379.
50. Nastala CL, Edington HD, McKinney TG,
Tahara H, Nalesnik MA, Brunda MJ, et al.
RecombinantIL-12 administration induces
tumor regression in association with
IFN-gamma production. Journal of Immunology
1994; 153:1697-1706.
51. Stagg J, Pommey S, Eliopoulos N, Galipeau J.
Interferon-gamma-stimulated marrow stromal
cells: a new type of nonhematopoietic
antigen-presenting cell. Blood 2006; 107:
2570-2577.
52. Ren G, Su J, Zhang L, Zhao X, Ling W, L’huillie
A, et al. Species variation in the mechanisms
of mesenchymal stem cell-mediated immunosuppression.
Stem Cells 2009;
27:1954-1962.
53. Der SD, Zhou A, Williams BR, Silverman RH.
Identification of genes differentially regulated
by interferon alpha, beta, or gamma
using oligonucleotide arrays. Proc Natl Acad
Sci USA 1998; 95: 15623-15628.
54. Miura Y, Tsujioka T, Nishimura Y, Sakaguchi
H, Maeda M, Hayashi H, et al. TRAIL expression
up-regulated by interferon-gamma via
phosphorylation of STAT1 induces myeloma
cell death. Anticancer Research 2006; 26:
4115-4124.
55. Lee J, Shin JS, Park JY, Kwon D, Choi SJ,
Kim SJ, et al. P38 mitogen-activated protein
kinase modulates expression of tumor necrosis
factor-related apoptosis inducing ligand
induced by interferon-gamma in fetal brain
astrocytes. J Neurosci Res 2003; 74:
884-890.
56. Almasan A, Ashkenazi A. Apo2L/TRAIL:
apoptosis signaling, biology, and potential
for cancer therapy. Cytokine and Growth Factor
Reviews 2003; 14: 337-348.
57. Grisendi G, Bussolari R, Cafarelli L, Petak I,
Rasini V, Veronesi E, et al. Adipose-derived
mesenchymal stem cells as stable source of
tumor necrosis factor-related apoptosis-inducing
ligand delivery for cancer therapy.
Cancer Res 2010; 70 (9): 3718-3729.
58. Du J, Zhou L, Chen X, Yan S, Ke M,Lu X,
Wang Z, Yu W, Xiang AP. IFN-γ primed
human bone marrow mesenchymal stem
cells induce tumor cell apoptosis in vitro via
tumor necrosis factor-related apoptosis-inducing
ligand. Int J Biochem Cell Biol 2012;
44: 1305-1314.
59. Sasportas LS, Kasmieh R, Wakimoto H, Hingtgen
S, van de Water JA, et al. Assessment
of therapeutic efficacy and fate of engineered
human mesenchymal stem cells for cancer
therapy. Proc Natl Acad Sci USA 2009; 106:
4822-4827.
60. Loebinger MR, Eddaoudi A, Davies D, Janes
SM. Mesenchymal stem cell delivery of
TRAIL can eliminate metastatic cancer.
Cancer Res 2009; 69: 4134-4142.
61. Widowati W, Murti H, Jasaputra DK, Sumitro
SB, Widodo MA, Fauziah N, Maesaroh M,
Bachtiar I. Selective Cytotoxic Potential of
IFN-γ and TNF-α on Breast Cancer Cell Lines
(T47D and MCF7), Asian J Cell Biol 2016; 11
(1): 1-12.