» Articles » PMID: 31574977

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

Overview
Journal J Clin Med
Specialty General Medicine
Date 2019 Oct 3
PMID 31574977
Citations 8
Authors
Affiliations
Soon will be listed here.
Abstract

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.

Citing Articles

A Comparison of Di- and Trinuclear Platinum Complexes Interacting with Glycosaminoglycans for Targeted Chemotherapy.

Katner S, Ginsburg E, Hampton J, Peterson E, Koblinski J, Farrell N ACS Med Chem Lett. 2023; 14(9):1224-1230.

PMID: 37736178 PMC: 10510529. DOI: 10.1021/acsmedchemlett.3c00244.


Genetics of enzymatic dysfunctions in metabolic disorders and cancer.

Mahe M, Rios-Fuller T, Karolin A, Schneider R Front Oncol. 2023; 13:1230934.

PMID: 37601653 PMC: 10433910. DOI: 10.3389/fonc.2023.1230934.


Multidimensional outlook on the pathophysiology of cervical cancer invasion and metastasis.

George N, Bhandari P, Shruptha P, Jayaram P, Chaudhari S, Satyamoorthy K Mol Cell Biochem. 2023; 478(11):2581-2606.

PMID: 36905477 PMC: 10006576. DOI: 10.1007/s11010-023-04686-3.


Investigation of the effects of overexpression of jumping translocation breakpoint (JTB) protein in MCF7 cells for potential use as a biomarker in breast cancer.

Jayathirtha M, Neagu A, Whitham D, Alwine S, Darie C Am J Cancer Res. 2022; 12(4):1784-1823.

PMID: 35530281 PMC: 9077082.


Exploitation of Sulfated Glycosaminoglycan Status for Precision Medicine of Triplatin in Triple-Negative Breast Cancer.

Hampton J, Peterson E, Katner S, Turner T, Alzubi M, Harrell J Mol Cancer Ther. 2021; 21(2):271-281.

PMID: 34815360 PMC: 8828673. DOI: 10.1158/1535-7163.MCT-20-0969.


References
1.
Alcaraz J, Mori H, Ghajar C, Brownfield D, Galgoczy R, Bissell M . Collective epithelial cell invasion overcomes mechanical barriers of collagenous extracellular matrix by a narrow tube-like geometry and MMP14-dependent local softening. Integr Biol (Camb). 2011; 3(12):1153-66. PMC: 3719864. DOI: 10.1039/c1ib00073j. View

2.
Lee Y, Park Y, Kwon M, Roh J, Choi S, Nam S . Expression of Lysyl Oxidase Predictive of Distant Metastasis of Laryngeal Cancer. Otolaryngol Head Neck Surg. 2017; 156(3):489-497. DOI: 10.1177/0194599816685698. View

3.
Johnston K, Lopez K . Lysyl oxidase in cancer inhibition and metastasis. Cancer Lett. 2018; 417:174-181. DOI: 10.1016/j.canlet.2018.01.006. View

4.
Demydchuk M, Hill C, Zhou A, Bunkoczi G, Stein P, Marchesan D . Insights into Hunter syndrome from the structure of iduronate-2-sulfatase. Nat Commun. 2017; 8:15786. PMC: 5472762. DOI: 10.1038/ncomms15786. View

5.
Dahal S, Huang P, Murray B, Mahler G . Endothelial to mesenchymal transformation is induced by altered extracellular matrix in aortic valve endothelial cells. J Biomed Mater Res A. 2017; 105(10):2729-2741. DOI: 10.1002/jbm.a.36133. View