Organotropism: New Insights into Molecular Mechanisms of Breast Cancer Metastasis

Overview

Journal NPJ Precis Oncol

Publisher Springer Nature

Specialty Oncology

Date 2018 Jun 7

PMID 29872722

Citations 175

Authors

Wenjing Chen

Andrew D Hoffmann

Huiping Liu

Xia Liu

Affiliations

Soon will be listed here.

Abstract

Metastasis accounts for 90% of breast cancer mortality. Despite the significant progress made over the past decade in cancer medicine our understanding of metastasis remains limited, therefore preventing and targeting metastasis is not yet possible. Breast cancer cells preferentially metastasize to specific organs, known as "organotropic metastasis", which is regulated by subtypes of breast cancer, host organ microenvironment, and cancer cells-organ interactions. The cross-talk between cancer cells and host organs facilitates the formation of the premetastatic niche and is augmented by factors released from cancer cells prior to the cancer cells' arrival at the host organ. Moreover, host microenvironment and specific organ structure influence metastatic niche formation and interactions between cancer cells and local resident cells, regulating the survival of cancer cells and formation of metastatic lesions. Understanding the molecular mechanisms of organotropic metastasis is essential for biomarker-based prediction and prognosis, development of innovative therapeutic strategy, and eventual improvement of patient outcomes. In this review, we summarize the molecular mechanisms of breast cancer organotropic metastasis by focusing on tumor cell molecular alterations, stemness features, and cross-talk with the host environment. In addition, we also update some new progresses on our understanding about genetic and epigenetic alterations, exosomes, microRNAs, circulating tumor cells and immune response in breast cancer organotropic metastasis.

Citing Articles

Lymphatic system is the mainstream for breast cancer dissemination and metastasis revealed by single-cell lineage tracing.

Miao K, Zhang A, Yang X, Zhang Y, Lin A, Wang L Mol Cancer. 2025; 24(1):75.

PMID: 40075470 PMC: 11899007. DOI: 10.1186/s12943-025-02279-w.

Drug Treatment Direction Based on the Molecular Mechanism of Breast Cancer Brain Metastasis.

Zhang Y, Shang H, Zhang J, Jiang Y, Li J, Xiong H Pharmaceuticals (Basel). 2025; 18(2).

PMID: 40006075 PMC: 11859690. DOI: 10.3390/ph18020262.

Synthesis and application of diazenyl sulfonamide-based schiff bases as potential BRCA2 active inhibitors against MCF-7 breast cancer cell line.

Rezaeianzadeh O, Asghari S, Tajbakhsh M, Khalilpour A, Shityakov S Sci Rep. 2025; 15(1):6661.

PMID: 39994448 PMC: 11850876. DOI: 10.1038/s41598-025-91113-w.

Molecular principles underlying aggressive cancers.

Nussinov R, Yavuz B, Jang H Signal Transduct Target Ther. 2025; 10(1):42.

PMID: 39956859 PMC: 11830828. DOI: 10.1038/s41392-025-02129-7.

Metabolic Reprogramming and Adaption in Breast Cancer Progression and Metastasis.

Zuo Q, Kang Y Adv Exp Med Biol. 2025; 1464():347-370.

PMID: 39821033 DOI: 10.1007/978-3-031-70875-6_17.

References

Na Y, Yoon Y, Son D, Seok S . Cyclooxygenase-2 inhibition blocks M2 macrophage differentiation and suppresses metastasis in murine breast cancer model. PLoS One. 2013; 8(5):e63451. PMC: 3646746. DOI: 10.1371/journal.pone.0063451. View

Mirza S, Jain N, Rawal R . Evidence for circulating cancer stem-like cells and epithelial-mesenchymal transition phenotype in the pleurospheres derived from lung adenocarcinoma using liquid biopsy. Tumour Biol. 2017; 39(3):1010428317695915. DOI: 10.1177/1010428317695915. View

Makki J . Diversity of Breast Carcinoma: Histological Subtypes and Clinical Relevance. Clin Med Insights Pathol. 2016; 8:23-31. PMC: 4689326. DOI: 10.4137/CPath.S31563. View

Olkhanud P, Baatar D, Bodogai M, Hakim F, Gress R, Anderson R . Breast cancer lung metastasis requires expression of chemokine receptor CCR4 and regulatory T cells. Cancer Res. 2009; 69(14):5996-6004. PMC: 2743688. DOI: 10.1158/0008-5472.CAN-08-4619. View

Yuksel U, Dilek G, Dogan L, Gulcelik M, Berberoglu U . The relationship between CSE1L expression and axillary lymph node metastasis in breast cancer. Tumori. 2015; 101(2):194-8. DOI: 10.5301/tj.5000239. View

Dilara Savci-Heijink C, Halfwerk H, Koster J, van de Vijver M . A novel gene expression signature for bone metastasis in breast carcinomas. Breast Cancer Res Treat. 2016; 156(2):249-59. PMC: 4819548. DOI: 10.1007/s10549-016-3741-z. View

Sihto H, Lundin J, Lundin M, Lehtimaki T, Ristimaki A, Holli K . Breast cancer biological subtypes and protein expression predict for the preferential distant metastasis sites: a nationwide cohort study. Breast Cancer Res. 2011; 13(5):R87. PMC: 3262199. DOI: 10.1186/bcr2944. View

Gil-Bernabe A, Ferjancic S, Tlalka M, Zhao L, Allen P, Im J . Recruitment of monocytes/macrophages by tissue factor-mediated coagulation is essential for metastatic cell survival and premetastatic niche establishment in mice. Blood. 2012; 119(13):3164-75. DOI: 10.1182/blood-2011-08-376426. View

Liu Y, Cao X . Characteristics and Significance of the Pre-metastatic Niche. Cancer Cell. 2016; 30(5):668-681. DOI: 10.1016/j.ccell.2016.09.011. View

10.

Gauld S, Dal Porto J, Cambier J . B cell antigen receptor signaling: roles in cell development and disease. Science. 2002; 296(5573):1641-2. DOI: 10.1126/science.1071546. View

11.

Kang Y, He W, Tulley S, Gupta G, Serganova I, Chen C . Breast cancer bone metastasis mediated by the Smad tumor suppressor pathway. Proc Natl Acad Sci U S A. 2005; 102(39):13909-14. PMC: 1236573. DOI: 10.1073/pnas.0506517102. View

12.

Monteiro A, Leal A, Goncalves-Silva T, Mercadante A, Kestelman F, Chaves S . T cells induce pre-metastatic osteolytic disease and help bone metastases establishment in a mouse model of metastatic breast cancer. PLoS One. 2013; 8(7):e68171. PMC: 3730734. DOI: 10.1371/journal.pone.0068171. View

13.

Wang L, Cossette S, Rarick K, Gershan J, Dwinell M, Harder D . Astrocytes directly influence tumor cell invasion and metastasis in vivo. PLoS One. 2013; 8(12):e80933. PMC: 3851470. DOI: 10.1371/journal.pone.0080933. View

14.

van der Weyden L, Arends M, Campbell A, Bald T, Wardle-Jones H, Griggs N . Genome-wide in vivo screen identifies novel host regulators of metastatic colonization. Nature. 2017; 541(7636):233-236. PMC: 5603286. DOI: 10.1038/nature20792. View

15.

Wilhelm I, Molnar J, Fazakas C, Hasko J, Krizbai I . Role of the blood-brain barrier in the formation of brain metastases. Int J Mol Sci. 2013; 14(1):1383-411. PMC: 3565326. DOI: 10.3390/ijms14011383. View

16.

Tomasello E, Vivier E . KARAP/DAP12/TYROBP: three names and a multiplicity of biological functions. Eur J Immunol. 2005; 35(6):1670-7. DOI: 10.1002/eji.200425932. View

17.

Onesti C, Vicier C, Andre F . What to expect from high throughput genomics in metastatic breast cancers?. Breast. 2015; 24 Suppl 2:S19-22. DOI: 10.1016/j.breast.2015.07.006. View

18.

Zhou W, Fong M, Min Y, Somlo G, Liu L, Palomares M . Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis. Cancer Cell. 2014; 25(4):501-15. PMC: 4016197. DOI: 10.1016/j.ccr.2014.03.007. View

19.

Lu X, Mu E, Wei Y, Riethdorf S, Yang Q, Yuan M . VCAM-1 promotes osteolytic expansion of indolent bone micrometastasis of breast cancer by engaging α4β1-positive osteoclast progenitors. Cancer Cell. 2011; 20(6):701-14. PMC: 3241854. DOI: 10.1016/j.ccr.2011.11.002. View

20.

Chaffer C, Weinberg R . A perspective on cancer cell metastasis. Science. 2011; 331(6024):1559-64. DOI: 10.1126/science.1203543. View