Inadequate tissue mineralization promotes cancer cell attachment

• Published in: PloS one Vol. 15; no. 8; p. e0237116
• Main Authors: Sariisik, Ediz, Zistl, Domenik, Docheva, Denitsa, Schilling, Arndt F, Benoit, Martin, Sudhop, Stefanie, Clausen-Schaumann, Hauke
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 28-08-2020; Public Library of Science (PLoS)
• Subjects: Adhesion; Applied physics; Attachment; Biology and Life Sciences; Biomimetics; Bone cancer; Bone demineralization; Calciferol; Calcification (Physiology); Cancer cells; Cancer metastasis; Cell adhesion; Cell adhesion & migration; Cell culture; Collagen; Collagens; Complications and side effects; Composite materials; Cytoskeleton; Dentin; Development and progression; Engineering and Technology; Experiments; Extracellular matrix; Fibrils; Fluorescence; Health aspects; Invasiveness; Lymph nodes; Lymphatic system; Medical prognosis; Medicine; Medicine and Health Sciences; Metabolism; Metastases; Metastasis; Microscopy; Mineralization; Nutrient deficiency; Prostate cancer; Proteins; Receptors; Research and Analysis Methods; Silicon nitride; Spectroscopy; Spectrum analysis; Structure; Supervision; Surgery; Tissue engineering; Tissues; Tumor cell lines; Vitamin D; Vitamin D deficiency; Vitamin deficiency; Germany; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0237116

Bone metastases are a frequent complication in prostate cancer, and several studies have shown that vitamin D deficiency promotes bone metastases. However, while many studies focus on vitamin D's role in cell metabolism, the effect of chronically low vitamin D levels on bone tissue, i.e. insufficient mineralization of the tissue, has largely been ignored. To investigate, whether poor tissue mineralization promotes cancer cell attachment, we used a fluorescence based adhesion assay and single cell force spectroscopy to quantify the adhesion of two prostate cancer cell lines to well-mineralized and demineralized dentin, serving as biomimetic bone model system. Adhesion rates of bone metastases-derived PC3 cells increased significantly on demineralized dentin. Additionally, on mineralized dentin, PC3 cells adhered mainly via membrane anchored surface receptors, while on demineralized dentin, they adhered via cytoskeleton-anchored transmembrane receptors, pointing to an interaction via exposed collagen fibrils. The adhesion rate of lymph node derived LNCaP cells on the other hand is significantly lower than that of PC3 and not predominately mediated by cytoskeleton-linked receptors. This indicates that poor tissue mineralization facilitates the adhesion of invasive cancer cells by the exposure of collagen and emphasizes the disease modifying effect of sufficient vitamin D for cancer patients.