Dormant but migratory tumour cells in desmoplastic stroma of invasive ductal carcinomas

Raviraj, V., Zhang, H., Chien, H.Y., Cole, L., Thompson, E.W., & Soon, L. (2012) Dormant but migratory tumour cells in desmoplastic stroma of invasive ductal carcinomas. Clinical and Experimental Metastasis, 29(3), pp. 273-292.

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Abstract

Mortality in breast cancer is linked to metastasis and recurrence yet there is no acceptable biological model for cancer relapse. We hypothesise that there might exist primary tumour cells capable of escaping surgery by migration and resisting radiotherapy and chemotherapy to cause cancer recurrence. We investigated this possibility in invasive ductal carcinoma (IDC) tissue and observed the presence of solitary primary tumour cells (SPCs) in the dense collagen stroma that encapsulates intratumoural cells (ICs). In IDC tissue sections, collagen was detected with either Masson's Trichrome or by second harmonics imaging. Cytokeratin-19 (CK-19) and vimentin (VIM) antibodies were, respectively, used to identify epithelial-derived tumour cells and to indicate epithelial to mesenchymal transition (EMT). Confocal/multiphoton microscopy showed that ICs from acini were mainly CK-19 +ve and were encapsulated by dense stromal collagen. Within the stroma, SPCs were detected by their staining for both CK-19 and VIM (confirming EMT). ICs and SPCs were subsequently isolated by laser capture microdissection followed by multiplex tandem-PCR studies. SPCs were found to be enriched for pro-migratory and anti-proliferative genes relative to ICs. In vitro experiments using collagen matrices at 20 mg/cm 3, similar in density to tumour matrices, demonstrated that SPC-like cells were highly migratory but dormant, phenotypes that recapitulated the genotypes of SPCs in clinical tissue. These data suggest that SPCs located at the breast cancer perimeter are invasive and dormant such that they may exceed surgical margins and resist local and adjuvant therapies. This study has important connotations for a role of SPCs in local recurrence.

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10 citations in Scopus
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11 citations in Web of Science®

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ID Code: 71911
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By (since 1996):4
Export Date: 6 May 2014
Source: Scopus
PubMed ID: 22271313
Additional URLs:
Keywords: Breast cancer, Cell migration, Dense stroma, Laser capture microdissection, Single cell dormancy, Tumour microenvironment
DOI: 10.1007/s10585-011-9450-4
ISSN: 1573-7276
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Deposited On: 21 May 2014 04:26
Last Modified: 22 May 2014 05:37

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