Article

Luminal breast cancer metastasis is dependent on estrogen signaling

Division of Medical Oncology, Department of Internal Medicine, UMDNJ-Robert Wood Johnson Medical School and The Cancer Institute of New Jersey, Room 2007, 195 Little Albany Street, New Brunswick, NJ 08903, USA.
Clinical and Experimental Metastasis (Impact Factor: 3.49). 03/2012; 29(5):493-509. DOI: 10.1007/s10585-012-9466-4
Source: PubMed

ABSTRACT

Luminal breast cancer is the most frequently encountered type of human breast cancer and accounts for half of all breast cancer deaths due to metastatic disease. We have developed new in vivo models of disseminated human luminal breast cancer that closely mimic the human disease. From initial lesions in the tibia, locoregional metastases develop predictably along the iliac and retroperitoneal lymph node chains. Tumors cells retain their epithelioid phenotype throughout the process of dissemination. In addition, systemically injected metastatic MCF-7 cells consistently give rise to metastases in the skeleton, floor of mouth, adrenal glands, as well as in the lungs, liver, brain and mammary fat pad. We show that growth of luminal breast cancer metastases is highly dependent on estrogen in a dose-dependent manner and that estrogen withdrawal induces rapid growth arrest of metastatic disease. On the other hand, even though micrometastases at secondary sites remain viable in the absence of estrogen, they are dormant and do not progress to macrometastases. Thus, homing to and seeding of secondary sites do not require estrogen. Moreover, in sharp contrast to basal-like breast cancer metastasis in which transforming growth factor-β signaling plays a key role, luminal breast cancer metastasis is independent of this cytokine. These findings have important implications for the development of targeted anti-metastatic therapy for luminal breast cancer.

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Available from: Vidya Ganapathy, Jun 12, 2014
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    • "The aberrant functions of TGF-β during breast cancer development may be linked to disease progression into various metastatic sites that also require TGF-β during formation, such as the brain (Dobolyi et al., 2012), liver (Karkampouna et al., 2012), lung (Bartram and Speer, 2004), and skeletal bone (Janssens et al., 2005). However, site specific organotropism is a complex process involving not only TGF-β but the tumor cell genotype and tumor–stroma interactions at the primary site and target organ (Lu and Kang, 2007; Eckhardt et al., 2012; Ganapathy et al., 2012). The various facets of each of these metastatic sites in conjunction with TGF-β are addressed elsewhere (Nishizuka et al., 2002; Lu and Kang, 2007; Drabsch and ten Dijke, 2011; Eckhardt et al., 2012). "
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Questions & Answers about this publication

  • Vidya Ganapathy added an answer in MCF-7 Cells:
    Does anybody have any experience with MCF-7 cells induced xenograft nude mice models?

    I need to induce tumors in nude mice models. I would wonder the cells cell counts to develop within 3 weeks. Does this count vary or similar to 3x10^7. Moreover I would need the detailed protocols regarding sample preparation after subculture, how to proceed/induced way?

    Vidya Ganapathy

    Please see attached paper. We have had a high success rate with MCF7 as you can see in this paper. I will be happy to help if you have more questions.

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      [Show abstract] [Hide abstract]
      ABSTRACT: Luminal breast cancer is the most frequently encountered type of human breast cancer and accounts for half of all breast cancer deaths due to metastatic disease. We have developed new in vivo models of disseminated human luminal breast cancer that closely mimic the human disease. From initial lesions in the tibia, locoregional metastases develop predictably along the iliac and retroperitoneal lymph node chains. Tumors cells retain their epithelioid phenotype throughout the process of dissemination. In addition, systemically injected metastatic MCF-7 cells consistently give rise to metastases in the skeleton, floor of mouth, adrenal glands, as well as in the lungs, liver, brain and mammary fat pad. We show that growth of luminal breast cancer metastases is highly dependent on estrogen in a dose-dependent manner and that estrogen withdrawal induces rapid growth arrest of metastatic disease. On the other hand, even though micrometastases at secondary sites remain viable in the absence of estrogen, they are dormant and do not progress to macrometastases. Thus, homing to and seeding of secondary sites do not require estrogen. Moreover, in sharp contrast to basal-like breast cancer metastasis in which transforming growth factor-β signaling plays a key role, luminal breast cancer metastasis is independent of this cytokine. These findings have important implications for the development of targeted anti-metastatic therapy for luminal breast cancer.
      Full-text · Article · Mar 2012 · Clinical and Experimental Metastasis
  • Vidya Ganapathy added an answer in Tumor Models:
    I am looking for developing consistent/reliable tumor model in mice with MCF7 cell line?

    I greatly appreciate your input

    Vidya Ganapathy

    You can look through this. We were quite successful in developing this model.

    • Source
      [Show abstract] [Hide abstract]
      ABSTRACT: Luminal breast cancer is the most frequently encountered type of human breast cancer and accounts for half of all breast cancer deaths due to metastatic disease. We have developed new in vivo models of disseminated human luminal breast cancer that closely mimic the human disease. From initial lesions in the tibia, locoregional metastases develop predictably along the iliac and retroperitoneal lymph node chains. Tumors cells retain their epithelioid phenotype throughout the process of dissemination. In addition, systemically injected metastatic MCF-7 cells consistently give rise to metastases in the skeleton, floor of mouth, adrenal glands, as well as in the lungs, liver, brain and mammary fat pad. We show that growth of luminal breast cancer metastases is highly dependent on estrogen in a dose-dependent manner and that estrogen withdrawal induces rapid growth arrest of metastatic disease. On the other hand, even though micrometastases at secondary sites remain viable in the absence of estrogen, they are dormant and do not progress to macrometastases. Thus, homing to and seeding of secondary sites do not require estrogen. Moreover, in sharp contrast to basal-like breast cancer metastasis in which transforming growth factor-β signaling plays a key role, luminal breast cancer metastasis is independent of this cytokine. These findings have important implications for the development of targeted anti-metastatic therapy for luminal breast cancer.
      Full-text · Article · Mar 2012 · Clinical and Experimental Metastasis