SDF-1-CXCR4 axis: Cell trafficking in the cancer stem cell niche of head and neck squamous cell carcinoma

Abstract

Stromal cell-derived factor-1α (SDF-1α), also known as CXCL12, has variable effects on a plurality of cells. CXCR4 has been identified as its corresponding receptor. 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 in the cancer stem cell niche. We evaluated the expression of CD44 as a cancer stem cell marker and of CXCR4 in human HNSCC tissue samples. Afterwards, we monitored the concentration of SDF-1 in peripheral blood samples of HNSCC patients and healthy donors. We showed that CD44 and CXCR4 are expressed in human HNSCC tissues. Markedly, CD44 showed a high expression in HNSCC cells bordering cancer stromal cells. CXCR4 was mainly expressed in HNSCC tumor nests, but not in the surrounding stromal cells. No significant difference was noted between the SDF-1 concentration in the peripheral blood of HNSCC patients compared to healthy donors. We showed that CD44, as a stem cell marker in HNSCC, is located mainly at the borderline of HNSCC tumor nests with the surrounding cells. In addition, we demonstrated that CXCR4 as the corresponding receptor to SDF-1 is highly expressed in HNSCC tumor nests, but not in the tumor stroma. We collected evidence that SDF-1-CXCR4 interaction may be a crucial pathway in cell trafficking in the cancer stem cell niche of HNSCC, while SDF-1 was not detected in the peripheral blood of HNSCC patients. The SDF-1-CXCR4 axis may play an important role in the cancer stem cell theory of HNSCC. As SDF-1α also exhibits a multitude of functional effects on HNSCC cells, such as migration and polarization, it may be possible that the SDF-1-CXCR4 axis is also involved in the pathophysiology of the progression, recurrence and metastasis of malignant disease. Understanding these interactions may help to gain further insight into these mechanisms and as such help to discover new strategies of therapy.

CXCL12-CXCR4 axis promotes the natural selection of breast cancer cell metastasis

“…One such chemokine is the ubiquitous CXCL12 which signals via the chemokine receptors CXCR4. The CXCR4-CXCL12 signaling axis contributes to metastasis and clinical outcomes in many different types of solid cancer, including breast cancer [28–33]. This receptor ligand pair appears to be involved in the directed migration of cancer cells to sites of metastasis, increased survival of cancer cells in sub-optimal conditions, and establishment of a tumor promoting cytokine/chemokine network.…”

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

“…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.…”

A central role for vesicle trafficking in epithelial neoplasia: intracellular highways to carcinogenesis

“…74, 80 Overall, the presentation of critical signaling receptors at the cell surface reflects a series of dynamic processes including the rate of de novo synthesis, endocytosis, recycling and degradation. In particular, the decision point between recycling and degradation can markedly revise the net presentation of receptors at the cell surface and the longevity of receptor signaling.…”