Short-term expansion of breast circulating cancer cells predicts response to anti-cancer therapy.

Khoo, BL; Lee, SC; Kumar, P; Tan, TZ; Warkiani, ME; Ow, SGW; Nandi, S; Lim, CT; Thiery, JP

Short-term expansion of breast circulating cancer cells predicts response to anti-cancer therapy.

Khoo, BL Lee, SC Kumar, P Tan, TZ Warkiani, ME Ow, SGW Nandi, S Lim, CT Thiery, JP

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Publisher:: IMPACT JOURNALS LLC
Publication Type:: Journal Article
Citation:: Oncotarget, 2015, 6, (17), pp. 15578-15593
Issue Date:: 2015-06-20

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Field	Value	Language
dc.contributor.author	Khoo, BL
dc.contributor.author	Lee, SC
dc.contributor.author	Kumar, P
dc.contributor.author	Tan, TZ
dc.contributor.author	Warkiani, ME
dc.contributor.author	Ow, SGW
dc.contributor.author	Nandi, S
dc.contributor.author	Lim, CT
dc.contributor.author	Thiery, JP
dc.date.accessioned	2023-03-12T23:05:32Z
dc.date.available	2015-04-24
dc.date.available	2023-03-12T23:05:32Z
dc.date.issued	2015-06-20
dc.identifier.citation	Oncotarget, 2015, 6, (17), pp. 15578-15593
dc.identifier.issn	1949-2553
dc.identifier.issn	1949-2553
dc.identifier.uri	http://hdl.handle.net/10453/167094
dc.description.abstract	Circulating tumor cells (CTCs) are considered as surrogate markers for prognosticating and evaluating patient treatment responses. Here, 226 blood samples from 92 patients with breast cancer, including patients with newly diagnosed or metastatic refractory cancer, and 16 blood samples from healthy subjects were cultured in laser-ablated microwells. Clusters containing an increasing number of cytokeratin-positive (CK+) cells appeared after 2 weeks, while most blood cells disappeared with time. Cultures were heterogeneous and exhibited two distinct sub-populations of cells: 'Small' (≤ 25 μm; high nuclear/cytoplasmic ratio; CD45-) cells, comprising CTCs, and 'Large' (> 25 μm; low nuclear/cytoplasmic ratio; CD68+ or CD56+) cells, corresponding to macrophage and natural killer-like cells. The Small cell fraction also showed copy number increases in six target genes (FGFR1, Myc, CCND1, HER2, TOP2A and ZNF217) associated with breast cancer. These expanded CTCs exhibited different proportions of epithelial-mesenchymal phenotypes and were transferable for further expansion as spheroids in serum-free suspension or 3D cultures. Cluster formation was affected by the presence and duration of systemic therapy, and its persistence may reflect therapeutic resistance. This novel and advanced method estimates CTC clonal heterogeneity and can predict, within a relatively short time frame, patient responses to therapy.
dc.format	Print
dc.language	eng
dc.publisher	IMPACT JOURNALS LLC
dc.relation.ispartof	Oncotarget
dc.relation.isbasedon	10.18632/oncotarget.3903
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	1112 Oncology and Carcinogenesis
dc.subject.mesh	Antineoplastic Agents
dc.subject.mesh	Biomarkers, Tumor
dc.subject.mesh	Breast Neoplasms
dc.subject.mesh	Cyclophosphamide
dc.subject.mesh	Doxorubicin
dc.subject.mesh	Drug Resistance, Neoplasm
dc.subject.mesh	Epithelial-Mesenchymal Transition
dc.subject.mesh	Female
dc.subject.mesh	Gene Dosage
dc.subject.mesh	Humans
dc.subject.mesh	Indoles
dc.subject.mesh	Keratins
dc.subject.mesh	MCF-7 Cells
dc.subject.mesh	Neoplastic Cells, Circulating
dc.subject.mesh	Pyrroles
dc.subject.mesh	Spheroids, Cellular
dc.subject.mesh	Sunitinib
dc.subject.mesh	Treatment Outcome
dc.subject.mesh	Tumor Cells, Cultured
dc.subject.mesh	Spheroids, Cellular
dc.subject.mesh	Tumor Cells, Cultured
dc.subject.mesh	Humans
dc.subject.mesh	Breast Neoplasms
dc.subject.mesh	Cyclophosphamide
dc.subject.mesh	Pyrroles
dc.subject.mesh	Indoles
dc.subject.mesh	Doxorubicin
dc.subject.mesh	Antineoplastic Agents
dc.subject.mesh	Treatment Outcome
dc.subject.mesh	Drug Resistance, Neoplasm
dc.subject.mesh	Gene Dosage
dc.subject.mesh	Female
dc.subject.mesh	Keratins
dc.subject.mesh	Neoplastic Cells, Circulating
dc.subject.mesh	Epithelial-Mesenchymal Transition
dc.subject.mesh	MCF-7 Cells
dc.subject.mesh	Biomarkers, Tumor
dc.subject.mesh	Sunitinib
dc.subject.mesh	Antineoplastic Agents
dc.subject.mesh	Biomarkers, Tumor
dc.subject.mesh	Breast Neoplasms
dc.subject.mesh	Cyclophosphamide
dc.subject.mesh	Doxorubicin
dc.subject.mesh	Drug Resistance, Neoplasm
dc.subject.mesh	Epithelial-Mesenchymal Transition
dc.subject.mesh	Female
dc.subject.mesh	Gene Dosage
dc.subject.mesh	Humans
dc.subject.mesh	Indoles
dc.subject.mesh	Keratins
dc.subject.mesh	MCF-7 Cells
dc.subject.mesh	Neoplastic Cells, Circulating
dc.subject.mesh	Pyrroles
dc.subject.mesh	Spheroids, Cellular
dc.subject.mesh	Sunitinib
dc.subject.mesh	Treatment Outcome
dc.subject.mesh	Tumor Cells, Cultured
dc.title	Short-term expansion of breast circulating cancer cells predicts response to anti-cancer therapy.
dc.type	Journal Article
utslib.citation.volume	6
utslib.location.activity	United States
utslib.for	1112 Oncology and Carcinogenesis
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Strength - IBMD - Initiative for Biomedical Devices
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
utslib.copyright.status	closed_access	*
dc.date.updated	2023-03-12T23:04:52Z
pubs.issue	17
pubs.publication-status	Published
pubs.volume	6
utslib.citation.issue	17

Abstract:

Circulating tumor cells (CTCs) are considered as surrogate markers for prognosticating and evaluating patient treatment responses. Here, 226 blood samples from 92 patients with breast cancer, including patients with newly diagnosed or metastatic refractory cancer, and 16 blood samples from healthy subjects were cultured in laser-ablated microwells. Clusters containing an increasing number of cytokeratin-positive (CK+) cells appeared after 2 weeks, while most blood cells disappeared with time. Cultures were heterogeneous and exhibited two distinct sub-populations of cells: 'Small' (≤ 25 μm; high nuclear/cytoplasmic ratio; CD45-) cells, comprising CTCs, and 'Large' (> 25 μm; low nuclear/cytoplasmic ratio; CD68+ or CD56+) cells, corresponding to macrophage and natural killer-like cells. The Small cell fraction also showed copy number increases in six target genes (FGFR1, Myc, CCND1, HER2, TOP2A and ZNF217) associated with breast cancer. These expanded CTCs exhibited different proportions of epithelial-mesenchymal phenotypes and were transferable for further expansion as spheroids in serum-free suspension or 3D cultures. Cluster formation was affected by the presence and duration of systemic therapy, and its persistence may reflect therapeutic resistance. This novel and advanced method estimates CTC clonal heterogeneity and can predict, within a relatively short time frame, patient responses to therapy.

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http://hdl.handle.net/10453/167094