Luminal breast cancer metastasis is dependent on estrogen signaling

Autor: Michael Reiss, Hilde H. Nienhuis, Whitney Banach-Petrosky, Vidya Ganapathy, Gregory D. Miles, Aparna Kareddula, Wen Xie
Přispěvatelé: Faculteit Medische Wetenschappen/UMCG
Jazyk: angličtina
Rok vydání: 2012
Předmět:
CA15-3
Cancer Research
Pathology
medicine.medical_treatment
Cell Communication
CELL-MIGRATION
UP-REGULATION
OSTEOBLASTIC BONE METASTASES
Metastasis
Immunoenzyme Techniques
Mice
Luminal breast cancer
Surgical oncology
Transforming Growth Factor beta
Tumor Cells
Cultured
Oligonucleotide Array Sequence Analysis
GENE-EXPRESSION
biology
MAMMARY-CARCINOMA
General Medicine
TUMOR DORMANCY OFFER
Transforming growth factor-beta
Cytokine
Oncology
Neoplasm Micrometastasis
Female
Signal Transduction
Cell signaling
medicine.medical_specialty
medicine.drug_class
Blotting
Western
FOCAL ADHESION KINASE
Mice
Nude
Bone Neoplasms
Breast Neoplasms
Real-Time Polymerase Chain Reaction
Article
RECEPTOR STATUS
Breast cancer
medicine
Biomarkers
Tumor
Animals
Humans
RNA
Messenger
Wound Healing
THERAPEUTIC TARGET
ENDOCRINE THERAPY
Gene Expression Profiling
Estrogens
Transforming growth factor beta
medicine.disease
Estrogen
biology.protein
Zdroj: Clinical & Experimental Metastasis, 29(5), 493-509. SPRINGER
ISSN: 0262-0898
Popis: 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-beta 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.
Databáze: OpenAIRE
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