Distinct phenotypes of cancer cells on tissue matrix gel

• Published in: Breast cancer research : BCR 2020-07, Vol.22 (1), p.82-82, Article 82
• Main Authors: Ruud, Kelsey F, Hiscox, William C, Yu, Ilhan, Chen, Roland K, Li, Weimin
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Antibodies; Atomic force microscopy; Bioengineering; Biology; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer; Cancer cells; Cell adhesion & migration; Cell culture; Cell Differentiation; Cell Line, Tumor; Cell Movement; Cell Proliferation; Collagen; Collagen (type I); Collagen - chemistry; Collagen Type I - chemistry; Connective tissue; Connective tissues; Differentiation; Drug Combinations; Epithelial cells; Extracellular matrix; Extracellular matrix (ECM); Extracellular Matrix - chemistry; Extracellular Matrix - metabolism; Extracellular Matrix - pathology; Extracellular Matrix Proteins - metabolism; Female; Fluorescence microscopy; Gene expression; Genetic aspects; Glycolysis; Humans; Hydrogel; Hydrogels; Hydrogels - chemistry; Lactates; Lactic acid; Laminin - chemistry; Mammary gland; Medical research; Microscopy; Microscopy, Atomic Force - methods; Mimicry; NMR; Nuclear magnetic resonance; Nuclear magnetic resonance spectroscopy; Penicillin; Phenotype; Phenotypes; Physiological aspects; Proteins; Proteoglycans - chemistry; Receptor; Spectroscopy; Statistical analysis; Stem cells; Swine; Tissue culture; Tissue matrix gel (TMG)
• ISSN: 1465-542X; 1465-5411; 1465-542X
• DOI: 10.1186/s13058-020-01321-7

Breast cancer cells invading the connective tissues outside the mammary lobule or duct immerse in a reservoir of extracellular matrix (ECM) that is structurally and biochemically distinct from that of their site of origin. The ECM is a spatial network of matrix proteins, which not only provide physical support but also serve as bioactive ligands to the cells. It becomes evident that the dimensional, mechanical, structural, and biochemical properties of ECM are all essential mediators of many cellular functions. To better understand breast cancer development and cancer cell biology in native tissue environment, various tissue-mimicking culture models such as hydrogel have been developed. Collagen I (Col I) and Matrigel are the most common hydrogels used in cancer research and have opened opportunities for addressing biological questions beyond the two-dimensional (2D) cell cultures. Yet, it remains unclear whether these broadly used hydrogels can recapitulate the environmental properties of tissue ECM, and whether breast cancer cells grown on CoI I or Matrigel display similar phenotypes as they would on their native ECM. We investigated mammary epithelial cell phenotypes and metabolic profiles on animal breast ECM-derived tissue matrix gel (TMG), Col I, and Matrigel. Atomic force microscopy (AFM), fluorescence microscopy, acini formation assay, differentiation experiments, spatial migration/invasion assays, proliferation assay, and nuclear magnetic resonance (NMR) spectroscopy were used to examine biological phenotypes and metabolic changes. Student's t test was applied for statistical analyses. Our data showed that under a similar physiological stiffness, the three types of hydrogels exhibited distinct microstructures. Breast cancer cells grown on TMG displayed quite different morphologies, surface receptor expression, differentiation status, migration and invasion, and metabolic profiles compared to those cultured on Col I and Matrigel. Depleting lactate produced by glycolytic metabolism of cancer cells abolished the cell proliferation promoted by the non-tissue-specific hydrogel. The full ECM protein-based hydrogel system may serve as a biologically relevant model system to study tissue- and disease-specific pathological questions. This work provides insights into tissue matrix regulation of cancer cell biomarker expression and identification of novel therapeutic targets for the treatment of human cancers based on tissue-specific disease modeling.