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

Faber, Anne; Hoermann, Karl; Stern‐Straeter, Jens; Schultz, David J.; Goessler, Ulrich Reinhart

doi:10.3892/or.2012.2171

Cited by 21 publications

(19 citation statements)

References 54 publications

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“…The mechanism in this work was not defined however they did report that the AHSG-associated migration activity of primary keratinocytes is largely independent of EGFR signaling and did not involve AKT1 or CDC42. However, Faber et al found that SDF-1α had great effect on migration in CD44þCXCR4þHNSCC cell lines [25, 26]. We recently showed that purified fetuin-A was a powerful chemo-attractant for breast and colon cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Alpha-2 Heremans Schmid Glycoprotein (AHSG) Modulates Signaling Pathways in Head and Neck Squamous Cell Carcinoma Cell Line SQ20B

Thompson

Sakwe

Koumangoye

et al. 2014

Experimental Cell Research

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This study was performed to identify the potential role of Alpha-2 Heremans Schmid Glycoprotein (AHSG) in Head and Neck Squamous Cell Carcinoma (HNSCC) tumorigenesis using an HNSCC cell line model. HNSCC cell lines are unique among cancer cell lines, in that they produce endogenous AHSG and do not rely, solely, on AHSG derived from serum. To produce our model, we performed a stable transfection to down-regulate AHSG in the HNSCC cell line SQ20B, resulting in three SQ20B sublines, AH50 with 50% AHSG production, AH20 with 20% AHSG production and EV which is the empty vector control expressing wild-type levels of AHSG. Utilizing these sublines, we examined the effect of AHSG depletion on cellular adhesion, proliferation, migration and invasion in a serum-free environment. We demonstrated that sublines EV and AH50 adhered to plastic and laminin significantly faster than the AH20 cell line, supporting the previously reported role of exogenous AHSG in cell adhesion. As for proliferative potential, EV had the greatest amount of proliferation with AH50 proliferation significantly diminished. AH20 cells did not proliferate at all. Depletion of AHSG also diminished cellular migration and invasion. TGF-β was examined to determine whether levels of the TGF-β binding AHSG influenced the effect of TGF-β on cell signaling and proliferation. Whereas higher levels of AHSG blunted TGF-β influenced SMAD and ERK signaling, it did not clearly affect proliferation, suggesting that AHSG influences on adhesion, proliferation, invasion and migration are primarily due to its role in adhesion and cell spreading. The previously reported role of AHSG in potentiating metastasis via protecting MMP-9 from autolysis was also supported in this cell line based model system of endogenous AHSG production in HNSCC. Together, these data show that endogenously produced AHSG in an HNSCC cell line, promotes in vitro cellular properties identified as having a role in tumorigenesis.

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Section: Discussionmentioning

confidence: 99%

Alpha-2 Heremans Schmid Glycoprotein (AHSG) Modulates Signaling Pathways in Head and Neck Squamous Cell Carcinoma Cell Line SQ20B

Thompson

Sakwe

Koumangoye

et al. 2014

Experimental Cell Research

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“…To give a few, selected examples: In gastric-CIC, flow-stimulated invasion was reduced by a blockade of CXCR4, SDF1, and/or CD44 (Kingsmore et al, 2016); in HNSCC, formation of podia and cell migration essentially depend on CD44 and CXCR4 expression (Faber et al, 2013). There is evidence that particularly CD44v6 contributes to CIC migration in response to SDF1.…”

Section: Cd44/cd44v6 Associations Contributing To Cic Motility and Inmentioning

confidence: 99%

CD44/CD44v6 a Reliable Companion in Cancer-Initiating Cell Maintenance and Tumor Progression

Wang

Zhao

Hackert

et al. 2018

Front. Cell Dev. Biol.

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Metastasis is the leading cause of cancer death, tumor progression proceeding through emigration from the primary tumor, gaining access to the circulation, leaving the circulation, settling in distant organs and growing in the foreign environment. The capacity of a tumor to metastasize relies on a small subpopulation of cells in the primary tumor, so called cancer-initiating cells (CIC). CIC are characterized by sets of markers, mostly membrane anchored adhesion molecules, CD44v6 being the most frequently recovered marker. Knockdown and knockout models accompanied by loss of tumor progression despite unaltered primary tumor growth unraveled that these markers are indispensable for CIC. The unexpected contribution of marker molecules to CIC-related activities prompted research on underlying molecular mechanisms. This review outlines the contribution of CD44, particularly CD44v6 to CIC activities. A first focus is given to the impact of CD44/CD44v6 to inherent CIC features, including the crosstalk with the niche, apoptosis-resistance, and epithelial mesenchymal transition. Following the steps of the metastatic cascade, we report on supporting activities of CD44/CD44v6 in migration and invasion. These CD44/CD44v6 activities rely on the association with membrane-integrated and cytosolic signaling molecules and proteases and transcriptional regulation. They are not restricted to, but most pronounced in CIC and are tightly regulated by feedback loops. Finally, we discuss on the engagement of CD44/CD44v6 in exosome biogenesis, loading and delivery. exosomes being the main acteurs in the long-distance crosstalk of CIC with the host. In brief, by supporting the communication with the niche and promoting apoptosis resistance CD44/CD44v6 plays an important role in CIC maintenance. The multifaceted interplay between CD44/CD44v6, signal transducing molecules and proteases facilitates the metastasizing tumor cell journey through the body. By its engagement in exosome biogenesis CD44/CD44v6 contributes to disseminated tumor cell settlement and growth in distant organs. Thus, CD44/CD44v6 likely is the most central CIC biomarker.

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“…The significance of the SDF-1-CXCR4 axis is well-discussed in the hematopoietic system. However, to the best of our knowledge, the present study was the first to show that HNSCC cells also demonstrate podia formation as a pre-condition for locomotion using dose-dependent migration towards an SDF-1 gradient (14). In summary, the SDF-1-CXCR4 axis may also play a crucial role in the development, progress, invasion and metastasis of HNSCC and may be an essential pathway in the interaction between CSCs in HNSCC and the surrounding supportive niche.…”

Section: Discussionmentioning

confidence: 68%

“…Clatot et al revealed that the intratumoral level of SDF-1 correlated with survival in HNSCC (32). By contrast, the concentration of SDF-1 in the peripheral blood of HNSCC patients was not observed to differ in comparison with healthy donors (14). The latter findings are consistent with the results of the present study, which suggest that the SDF-1-CXCR4 axis may be involved in the CSC niche within the tumor, but not in the periphery of the blood system.…”

Section: Discussionmentioning

confidence: 87%

“…The cytokine arises in two isoforms, SDF-1α (24–88 amino acids) and SDF-1β (24–93 amino acids) by alternative splicing (10,12,13). SDF-1 has been shown to be a potent chemoattractant for hematopoietic progenitor cells (HPCs) and induces directional locomotion and podia formation in HNSCC in a dose-dependent manner (14). Therefore, SDF-1 is considered to be one of the key regulators for HPC trafficking between the peripheral blood circulation, bone marrow (9,10,15,16) and in the CSC niche of HNSCC.…”

Section: Introductionmentioning

confidence: 99%

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Interaction of a CD44+ head and neck squamous cell carcinoma cell line with a stromal cell-derived factor-1-expressing supportive niche: An in vitro model

et al. 2013

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The cancer stem cell (CSC) theory implies that CSCs are surrounded by supportive stromal cells, which are known as the CSC niche. Stromal cell-derived factor-1 (SDF-1) shows a multitude of functional effects in head and neck squamous cell carcinoma (HNSCC) cells, including migration and polarization. Therefore, the SDF-1-CXCR4 axis may be involved in the pathophysiology of the progression, recurrence and metastasis of malignant diseases of the head and neck. In the present study, the CD44+ HNSCC UM-SCC-11A cell line was used as a model for CSCs. The interaction between the UM-SCC-11A cells and the supportive microenvironmental cells, including fibrocytes, human umbilical vein endothelial cells (HUVECs) and human microvascular vein endothelial cells (HMVECs) was evaluated. All the cell types that were tested were shown to secrete different concentrations of SDF-1 into the surrounding culture medium [mean (m)fibro, 1243.3±156.2 pg/ml; mHMVEC, 1061.4±23.2 pg/ml; mHUVEC, 849.6±110.9 pg/ml]. The migration of the UM-SCC-11A cells towards the supportive cells was increased by a higher supply of SDF-1 (contrfibro, 315.23±61.55 μm; mfibro, 477.73±143.7 μm; Pfibro=0.003; contrHMVEC, 123.41±66.68 μm; mHMVEC, 249.04±111.95 μm; PHMVEC=0.004; contrHUVEC, 189.7±93.26 μm; mHUVEC, 260.82±161.58 μm). The amount of the UM-SCC-11A cells that migrated towards the differentiated fibrocytes was significantly higher than that which migrated towards the HMVECs or HUVECs (Pfibro/HMVEC=2.12E-11; Pfibro/HUVEC=2.28E-5). Cell-cell interaction by podia formation of the UM-SCC-11A cells was observed in all the supportive cell types that were tested. Broadly based cell-cell contacts were observed. By contrast, digitiform podia formations presented by the UM-SCC-11A cells were determined using fluorescence microscopy. The SDF-1-CXCR4 axis is postulated to be a crucial pathway in the interaction between CSCs and their surrounding supportive cells. Understanding the cell-cell interactions in the CSC niche using in vitro models may aid in gaining further insight into these mechanisms and finding new strategies of therapy in this field.

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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

Cited by 21 publications

References 54 publications

Alpha-2 Heremans Schmid Glycoprotein (AHSG) Modulates Signaling Pathways in Head and Neck Squamous Cell Carcinoma Cell Line SQ20B

Alpha-2 Heremans Schmid Glycoprotein (AHSG) Modulates Signaling Pathways in Head and Neck Squamous Cell Carcinoma Cell Line SQ20B

CD44/CD44v6 a Reliable Companion in Cancer-Initiating Cell Maintenance and Tumor Progression

Interaction of a CD44+ head and neck squamous cell carcinoma cell line with a stromal cell-derived factor-1-expressing supportive niche: An in vitro model

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