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A Novel Ex Vivo System Using 3D Polymer Scaffold to Culture Circulating Tumor Cells from Breast Cancer Patients Exhibits Dynamic E-M Phenotypes

De, Tamasa and Goyal, Shina and Balachander, Gowri and Chatterjee, Kaushik and Kumar, Prashant and Babu, Govind K and Rangarajan, Annapoorni (2019) A Novel Ex Vivo System Using 3D Polymer Scaffold to Culture Circulating Tumor Cells from Breast Cancer Patients Exhibits Dynamic E-M Phenotypes. In: JOURNAL OF CLINICAL MEDICINE, 8 (9).

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Official URL: http:/dx.doi.org/10.3390/jcm8091473


The majority of the cancer-associated deaths is due to metastasis-the spread of tumors to other organs. Circulating tumor cells (CTCs), which are shed from the primary tumor into the circulation, serve as precursors of metastasis. CTCs have now gained much attention as a new prognostic and diagnostic marker, as well as a screening tool for patients with metastatic disease. However, very little is known about the biology of CTCs in cancer metastasis. An increased understanding of CTC biology, their heterogeneity, and interaction with other cells can help towards a better understanding of the metastatic process, as well as identify novel drug targets. Here we present a novel ex vivo 3D system for culturing CTCs from breast cancer patient blood samples using porous poly(epsilon-caprolactone) (PCL) scaffolds. As a proof of principle study, we show that ex vivo culture of 12/16 (75%) advanced stage breast cancer patient blood samples were enriched for CTCs identified as CK+ (cytokeratin positive) and CD45- (CD45 negative) cells. The deposition of extracellular matrix proteins on the PCL scaffolds permitted cellular attachment to these scaffolds. Detection of Ki-67 and bromodeoxyuridine (BrdU) positive cells revealed proliferating cell population in the 3D scaffolds. The CTCs cultured without prior enrichment exhibited dynamic differences in epithelial (E) and mesenchymal (M) composition. Thus, our 3D PCL scaffold system offers a physiologically relevant model to be used for studying CTC biology as well as for individualized testing of drug susceptibility. Further studies are warranted for longitudinal monitoring of epithelial-mesenchymal transition (EMT) in CTCs for clinical association.

Item Type: Journal Article
Publisher: MDPI
Additional Information: Copyright of this article belongs to MDPI
Keywords: circulating tumor cells (CTCs); breast cancer; 3D culture; epithelial-mesenchymal heterogeneity
Department/Centre: Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Division of Mechanical Sciences > Materials Engineering (formerly Metallurgy)
Date Deposited: 03 Dec 2019 10:41
Last Modified: 03 Dec 2019 10:41
URI: http://eprints.iisc.ac.in/id/eprint/63862

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