Cancer cells grown in 3D under fluid flow exhibit an aggressive phenotype and reduced responsiveness to the anti-cancer treatment doxorubicin.

Abstract

3D laboratory models of cancer are designed to recapitulate the biochemical and biophysical characteristics of the tumour microenvironment and aim to enable studies of cancer, and new therapeutic modalities, in a physiologically-relevant manner. We have developed an in vitro 3D model comprising a central high-density mass of breast cancer cells surrounded by collagen type-1 and we incorporated fluid flow and pressure. We noted significant changes in cancer cell behaviour using this system. MDA-MB231 and SKBR3 breast cancer cells grown in 3D downregulated the proliferative marker Ki67 (P < 0.05) and exhibited decreased response to the chemotherapeutic agent doxorubicin (DOX) (P < 0.01). Mesenchymal markers snail and MMP14 were upregulated in cancer cells maintained in 3D (P < 0.001), cadherin-11 was downregulated (P < 0.001) and HER2 increased (P < 0.05). Cells maintained in 3D under fluid flow exhibited a further reduction in response to DOX (P < 0.05); HER2 and Ki67 levels were also attenuated. Fluid flow and pressure was associated with reduced cell viability and decreased expression levels of vimentin. In summary, aggressive cancer cell behaviour and reduced drug responsiveness was observed when breast cancer cells were maintained in 3D under fluid flow and pressure. These observations are relevant for future developments of 3D in vitro cancer models and organ-on-a-chip initiatives.

• Authors: Tayebeh Azimi, Marilena Loizidou, Miriam V Dwek
• Journal: Scientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 12020 (07 21 2020) ISSN: 2045-2322 [Electronic] England
• PMID: 32694700 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Cadherins
• Ki-67 Antigen
• MKI67 protein, human
• SNAI1 protein, human
• Snail Family Transcription Factors
• VIM protein, human
• Vimentin
• osteoblast cadherin
• Doxorubicin
• ERBB2 protein, human
• Receptor, ErbB-2
• MMP14 protein, human
• Matrix Metalloproteinase 14

Topics

• Antineoplastic Agents (pharmacology)
• Cadherins (analysis, metabolism)
• Cell Culture Techniques (methods)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Doxorubicin (pharmacology)
• Drug Resistance, Neoplasm (drug effects)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Ki-67 Antigen (analysis, metabolism)
• Matrix Metalloproteinase 14 (analysis, metabolism)
• Models, Biological
• Phenotype
• Receptor, ErbB-2 (analysis, metabolism)
• Snail Family Transcription Factors (analysis, metabolism)
• Triple Negative Breast Neoplasms (pathology)
• Tumor Microenvironment
• Vimentin (analysis, metabolism)