Fusion of CCL21 non-migratory active breast epithelial and breast cancer cells give rise to CCL21 migratory active tumor hybrid cell lines

• Published in: PloS one Vol. 8; no. 5; p. e63711
• Main Authors: Berndt, Benjamin, Haverkampf, Sonja, Reith, Georg, Keil, Silvia, Niggemann, Bernd, Zänker, Kurt S, Dittmar, Thomas
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07-05-2013; Public Library of Science (PLoS)
• Subjects: Biology; Biotechnology; Breast cancer; Breast Neoplasms - pathology; Calcium; Calcium - metabolism; Calcium influx; Cancer; Cancer cells; Cancer metastasis; Cascades; CC chemokine receptors; CCL21 protein; CCR7 protein; Cell Fusion; Cell Line, Tumor; Cell migration; Cell Movement - drug effects; Cellular signal transduction; Chemokine CCL21 - pharmacology; Chemokines; Cytometry; Dendritic cells; Drug resistance; Education; Epithelial cells; Epithelial Cells - drug effects; Epithelial Cells - pathology; Female; Flow cytometry; Gene Knockdown Techniques; Humans; Hybrid Cells - drug effects; Hybrid Cells - pathology; Immunology; Invasiveness; Kinases; Kinetics; Ligands; Lymph nodes; Lymphatic system; Medicine; Melanoma; Metastases; Metastasis; Multiple myeloma; Phosphorylation; Prostate cancer; Proteins; Receptors, CCR7 - metabolism; Recruitment; Rodents; Signal transduction; Signal Transduction - drug effects; Signaling; siRNA; Stem cells; Transduction; Tumor cell lines; Tumor cells
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0063711

The biological phenomenon of cell fusion has been linked to tumor progression because several data provided evidence that fusion of tumor cells and normal cells gave rise to hybrid cell lines exhibiting novel properties, such as increased metastatogenic capacity and an enhanced drug resistance. Here we investigated M13HS hybrid cell lines, derived from spontaneous fusion events between M13SV1-EGFP-Neo breast epithelial cells exhibiting stem cell characteristics and HS578T-Hyg breast cancer cells, concerning CCL21/CCR7 signaling. Western Blot analysis showed that all cell lines varied in their CCR7 expression levels as well as differed in the induction and kinetics of CCR7 specific signal transduction cascades. Flow cytometry-based calcium measurements revealed that a CCL21 induced calcium influx was solely detected in M13HS hybrid cell lines. Cell migration demonstrated that only M13HS hybrid cell lines, but not parental derivatives, responded to CCL21 stimulation with an increased migratory activity. Knockdown of CCR7 expression by siRNA completely abrogated the CCL21 induced migration of hybrid cell lines indicating the necessity of CCL21/CCR7 signaling. Because the CCL21/CCR7 axis has been linked to metastatic spreading of breast cancer to lymph nodes we conclude from our data that cell fusion could be a mechanism explaining the origin of metastatic cancer (hybrid) cells.