Organ-selective chemoresistance in metastasis from human breast cancer cells: inhibition of apoptosis, genetic variability and microenvironment at the metastatic focus - PubMed (original) (raw)
Comparative Study
. 2004 Dec;25(12):2293-301.
doi: 10.1093/carcin/bgh272. Epub 2004 Sep 3.
Affiliations
- PMID: 15347599
- DOI: 10.1093/carcin/bgh272
Comparative Study
Organ-selective chemoresistance in metastasis from human breast cancer cells: inhibition of apoptosis, genetic variability and microenvironment at the metastatic focus
Bin Gu et al. Carcinogenesis. 2004 Dec.
Abstract
We hypothesized that the development of the most resistant cells during metastasis is favored by anti-apoptotic proteins, leading to the acquisition of an adaptive phenotype crucial to drug resistance at the metastatic foci. In order to test it, we induced metastasis in nude mice, injecting orthotopicaly 435/Bcl-x(L) or 435/Neo cells, transfected previously with the luciferase gene to use it as a tumor marker, and treated them with a therapeutic dose of docetaxel. We monitored metastasis in mice by calculating tumor cell equivalents (TCEs) present in tissues. Between docetaxel-treated and non-treated 435/Bcl-x(L).luc mice significant differences in the metastatic burden of lymph nodes (P = 0.02) and viscera (P = 0.02) were observed. However, treatment did not significantly decrease metastatic burden in bones (P = 0.19). Additionally, we analyzed the clonality of metastasis from lung, bone and lymph node by genomic DNA fingerprinting. Bcl-x(L) enhanced cell genetic instability in terms of gain and loss fractions (GF = 0.18 and LF = -0.21) when compared with the control 435/Neo (GF = 0.15 and LF = -0.14). Thus, genetic instability might be a molecular mechanism favored by Bcl-x(L) evolved in the selection process of breast cancer progression, which results in different genetic changes among metastases from lung, bone or lymph node, favoring organ-selective chemoresistance.
Similar articles
- Overexpression of Bcl-xL in human breast cancer cells enhances organ-selective lymph node metastasis.
España L, Fernández Y, Rubio N, Torregrosa A, Blanco J, Sierra A. España L, et al. Breast Cancer Res Treat. 2004 Sep;87(1):33-44. doi: 10.1023/B:BREA.0000041579.51902.89. Breast Cancer Res Treat. 2004. PMID: 15377849 - Bcl-x(L)-mediated changes in metabolic pathways of breast cancer cells: from survival in the blood stream to organ-specific metastasis.
España L, Martín B, Aragüés R, Chiva C, Oliva B, Andreu D, Sierra A. España L, et al. Am J Pathol. 2005 Oct;167(4):1125-37. doi: 10.1016/S0002-9440(10)61201-1. Am J Pathol. 2005. PMID: 16192647 Free PMC article. - Bcl-xL promotes metastasis of breast cancer cells by induction of cytokines resistance.
Fernández Y, España L, Mañas S, Fabra A, Sierra A. Fernández Y, et al. Cell Death Differ. 2000 Apr;7(4):350-9. doi: 10.1038/sj.cdd.4400662. Cell Death Differ. 2000. PMID: 10773819 - Long-term suppression of lymphangitic lung metastasis from breast cancer using biweekly docetaxel: a case report.
Ninomiya J, Horiguchi J, Koibuchi Y, Yoshida T, Iijima K, Yoshida M, Takata D, Yokoe T, Iino Y, Morishita Y. Ninomiya J, et al. Breast Cancer. 2003;10(4):361-5. doi: 10.1007/BF02967658. Breast Cancer. 2003. PMID: 14634516 Review. - Organ tropism in solid tumor metastasis: an updated review.
Mortezaee K. Mortezaee K. Future Oncol. 2021 May;17(15):1943-1961. doi: 10.2217/fon-2020-1103. Epub 2021 Mar 17. Future Oncol. 2021. PMID: 33728946 Review.
Cited by
- The bone microenvironment promotes tumor growth and tissue perfusion compared with striated muscle in a preclinical model of prostate cancer in vivo.
Mussawy H, Viezens L, Schroeder M, Hettenhausen S, Sündermann J, Wellbrock J, Kossow K, Schaefer C. Mussawy H, et al. BMC Cancer. 2018 Oct 16;18(1):979. doi: 10.1186/s12885-018-4905-5. BMC Cancer. 2018. PMID: 30326868 Free PMC article. - Therapeutic Antibody Targeting Tumor- and Osteoblastic Niche-Derived Jagged1 Sensitizes Bone Metastasis to Chemotherapy.
Zheng H, Bae Y, Kasimir-Bauer S, Tang R, Chen J, Ren G, Yuan M, Esposito M, Li W, Wei Y, Shen M, Zhang L, Tupitsyn N, Pantel K, King C, Sun J, Moriguchi J, Jun HT, Coxon A, Lee B, Kang Y. Zheng H, et al. Cancer Cell. 2017 Dec 11;32(6):731-747.e6. doi: 10.1016/j.ccell.2017.11.002. Cancer Cell. 2017. PMID: 29232552 Free PMC article. - Targeting metastasis.
Steeg PS. Steeg PS. Nat Rev Cancer. 2016 Apr;16(4):201-18. doi: 10.1038/nrc.2016.25. Nat Rev Cancer. 2016. PMID: 27009393 Free PMC article. Review. - Expression of endoplasmic reticulum stress proteins is a candidate marker of brain metastasis in both ErbB-2+ and ErbB-2- primary breast tumors.
Sanz-Pamplona R, Aragüés R, Driouch K, Martín B, Oliva B, Gil M, Boluda S, Fernández PL, Martínez A, Moreno V, Acebes JJ, Lidereau R, Reyal F, Van de Vijver MJ, Sierra A. Sanz-Pamplona R, et al. Am J Pathol. 2011 Aug;179(2):564-79. doi: 10.1016/j.ajpath.2011.04.037. Epub 2011 Jun 25. Am J Pathol. 2011. PMID: 21708117 Free PMC article. - Effects of clusterin over-expression on metastatic progression and therapy in breast cancer.
Flanagan L, Whyte L, Chatterjee N, Tenniswood M. Flanagan L, et al. BMC Cancer. 2010 Mar 22;10:107. doi: 10.1186/1471-2407-10-107. BMC Cancer. 2010. PMID: 20307318 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials