Document Detail


A preclinical mouse model of invasive lobular breast cancer metastasis.
MedLine Citation:
PMID:  23151903     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Metastatic disease accounts for over 90% of cancer-related deaths, but the development of effective anti-metastatic agents has been hampered by the paucity of clinically relevant preclinical models of human metastatic disease. Here we report the development of a mouse model of spontaneous breast cancer metastasis which recapitulates key events in its formation and clinical course. Specifically, using the conditional K14cre;Cdh1F/F;Trp53F/F model of de novo mammary tumor formation, we orthotopically transplanted invasive lobular carcinoma (mILC) fragments into mammary glands of wild-type syngeneic hosts. Once primary tumors were established in recipient mice, we mimicked the clinical course of treatment by performing a mastectomy. After surgery, recipient mice succumbed to widespread overt metastatic disease in lymph nodes, lungs and gastrointestinal tract. Genomic profiling of paired mammary tumors and distant metastases showed that our model provides a unique tool to further explore the biology of metastatic disease. Neoadjuvant and adjuvant intervention studies using standard-of-care chemotherapeutics demonstrated the value of this model in determining therapeutic agents that can target early and late-stage metastatic disease. In obtaining a more accurate preclinical model of metastatic lobular breast cancer, our work offers advances supporting the development of more effective treatment strategies for metastatic disease.
Authors:
Chris W Doornebal; Sjoerd Klarenbeek; Tanya M Braumuller; Christiaan N Klijn; Metamia Ciampricotti; Cheei-Sing Hau; Markus W Hollmann; Jos Jonkers; Karin E de Visser
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-14
Journal Detail:
Title:  Cancer research     Volume:  -     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Division of Immunology, The Netherlands Cancer Institute.
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