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Article

Iduronate-2-Sulfatase-Regulated Dermatan Sulfate Levels Potentiate the Invasion of Breast Cancer Epithelia through Collagen Matrix

1
Department of Molecular Reproduction Development and Genetics, Indian Institute of Science, Bangalore 560012, India
2
Department of Electrical Communications and Engineering, Indian Institute of Science, Bangalore 560012 India
3
Department of Pathology, Kidwai Memorial Institute of Oncology, Bangalore 560029, India
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(10), 1562; https://doi.org/10.3390/jcm8101562
Received: 7 July 2019 / Revised: 26 August 2019 / Accepted: 27 August 2019 / Published: 30 September 2019
Cancer epithelia show elevation in levels of sulfated proteoglycans including dermatan sulfates (DS). The effect of increased DS on cancer cell behavior is still unclear. We hypothesized that decreased expression of the enzyme Iduronate-2-sulfatase (IDS) can lead to increased DS levels, which would enhance the invasion of cancer cells. Breast cancer sections shows depleted IDS levels in tumor epithelia, when compared with adjacent untransformed breast tissues. IDS signals showed a progressive decrease in the non-transformed HMLE, transformed but non-invasive MCF-7 and transformed and invasive MDA-MB-231 cells, respectively, when cultured on Type 1 collagen scaffolds. DS levels measured by ELISA increased in an inverse-association with IDS levels. Knockdown of IDS in MCF-7 epithelia also increased the levels of DS. MCF-7 cells with depleted IDS expression, when imaged using two photon-excited fluorescence and second harmonic generation microscopy, exhibited a mesenchymal morphology with multiple cytoplasmic projections compared with epithelioid control cells, interacted with their surrounding matrix, and showed increased invasion through Type 1 collagen matrices. Both these traits were phenocopied when control MCF-7 cells were cultivated on Type 1 collagen gels polymerized in the presence of DS. In monolayer cultures, DS had no effect on MCF-7 migration. In the context of our demonstration that DS enhances the elastic modulus of Type 1 collagen gels, we propose that a decrease of IDS expression leads to accumulation within cancer epithelia of DS: the latter remodels the collagen around cancer cells leading to changes in cell shape and invasiveness through fibrillar matrix milieu. View Full-Text
Keywords: dermatan sulfate; breast cancer; iduronate-2-sulfatase dermatan sulfate; breast cancer; iduronate-2-sulfatase
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MDPI and ACS Style

Singh, V.; Jha, K.K.; M, J.K.; Kumar, R.V.; Raghunathan, V.; Bhat, R. Iduronate-2-Sulfatase-Regulated Dermatan Sulfate Levels Potentiate the Invasion of Breast Cancer Epithelia through Collagen Matrix. J. Clin. Med. 2019, 8, 1562. https://doi.org/10.3390/jcm8101562

AMA Style

Singh V, Jha KK, M JK, Kumar RV, Raghunathan V, Bhat R. Iduronate-2-Sulfatase-Regulated Dermatan Sulfate Levels Potentiate the Invasion of Breast Cancer Epithelia through Collagen Matrix. Journal of Clinical Medicine. 2019; 8(10):1562. https://doi.org/10.3390/jcm8101562

Chicago/Turabian Style

Singh, Vishal, Keshav K. Jha, Jyothsna K. M, Rekha V. Kumar, Varun Raghunathan, and Ramray Bhat. 2019. "Iduronate-2-Sulfatase-Regulated Dermatan Sulfate Levels Potentiate the Invasion of Breast Cancer Epithelia through Collagen Matrix" Journal of Clinical Medicine 8, no. 10: 1562. https://doi.org/10.3390/jcm8101562

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