Progress towards understanding heterotypic interactions in multi-culture models of breast cancer.
Microenvironments in primary tumors and metastases include multiple cell types whose dynamic and reciprocal interactions are central to progression of the disease. However, the literature involving breast cancer studied in vitro is dominated by cancer cells in mono-culture or co-cultured with one other cell type. For in vitro studies of breast cancer the inclusion of multiple cell types has led to models that are more representative of in vivo behaviors and functions as compared to more traditional monoculture. Here, we review foundational co-culture techniques and their adaptation to multi-culture (including three or more cell types). Additionally, while macroscale methods involving conditioned media, direct contact, and indirect interactions have been informative, we examined many advances that have been made more recently using microscale systems with increased control over cellular and structural complexity. Throughout this discussion we consider the benefits and limitations of current multi-culture methods and the significant results they have produced.
Wisconsin Institutes for Medical Research, University of Wisconsin-Madison, Madison, Wisconsin, USA. djbeebe@wisc.edu.
Mary C
MC
Regier
Elaine T
ET
Alarid
David J
DJ
Beebe
D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D063646:Carcinogenesis; D002450:Cell Communication; D002454:Cell Differentiation; D018920:Coculture Techniques / Q000379:methods*; D005260:Female; D006801:Humans; D014411:Neoplastic Stem Cells / Q000473:pathology* / Q000502:physiology*; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment / Q000502:physiology*