title: Functional effects of SDF-1α on a CD44(+) CXCR4(+) squamous cell carcinoma cell line as a model for interactions in the cancer stem cell niche.
abstract: Stromal cell-derived factor-1α (SDF-1α), also known as CXCL12, has variable effects on a plurality of cells. It is known to have selective effects on cell migration, morphology, survival and cell homing. As such the SDF-1-CXCR4 axis is postulated to be a crucial key pathway in the interaction between (cancer) stem cells and their surrounding supportive cells, the so-called (cancer) stem cell niche. We evaluated the expression of CD44 as a cancer stem cell (CSC) marker and the expression of CXCR4 in the head and neck squamous cell carcinoma (HNSCC) cell line UM-SCC 11A. In addition, we monitored proliferation, formation of podia and migration of UM-SCC 11A cells under the influence of SDF-1α. Whereas SDF-1α induced the formation of podia of CD44(+) CXCR4(+) UM-SCC 11A cells in a dose-dependent manner and the maximum number of cells exhibiting the formation of podia was observed under the influence of 10 ng/ml SDF-1α (P=5.3x10(-6)), the highest number of migrating cells was noted using a concentration of 100 ng/ml (P=0.027). Proliferation and survival were not affected by SDF-1α. We showed that UM-SCC 11A cells could be a target for SDF-1α by CXCR4 expression and these cells also showed characteristics of HNSCC CSCs via CD44 expression. We demonstrated that SDF-1α is a chemoattractant for UM-SCC 11A cells, and a maximum directed migration was achieved under the influence of 100 ng/ml SDF-1α. Changes in cell morphology by presenting filopodia or a prominent uropod were noted following treatment of 10 ng/ml SDF-1α. The SDF-CXCR4 axis may play a crucial role in the interaction between CSCs and their supportive cells in the CSC niche. Understanding these interactions may help to gain further insight into the pathophysiology of the progression and recurrence of malignant diseases and thus help to develop novel strategies for therapy.
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, University Medical Centre Mannheim, 68167 Mannheim, Germany. faberanne@gmx.de
authors.forename: Anne
authors.initials: A
authors.lastname: Faber
authors.forename: Karl
authors.initials: K
authors.lastname: Hoermann
authors.forename: Jens
authors.initials: J
authors.lastname: Stern-Straeter
authors.forename: David Johannes
authors.initials: DJ
authors.lastname: Schultz
authors.forename: Ulrich Reinhart
authors.initials: UR
authors.lastname: Goessler
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D016764:Cell Polarity / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D008954:Models, Biological; D014411:Neoplastic Stem Cells; D011554:Pseudopodia / Q000187:drug effects; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015398:Signal Transduction; D055153:Stem Cell Niche
chemical_list: C497483:CD44 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D018960:Hyaluronan Receptors; D019718:Receptors, CXCR4