The CXCL12-CXCR4 signaling axis plays a key role in cancer metastasis and is a potential target for developing novel therapeutics against metastatic cancer.
The expression of macrophage markers (CD163, CCL2/CCR2, CSF1/CSFR1, CXCR4/CXCL12), protumorigenic toll-like receptor pathway genes (CD14/TLR-1,-2,-4,-5,-6/MyD88), HLA-E, ecto-nuclease CD73/NT5E and inhibitory complement receptors (CD-59,-55,-46) remained high in metastases and represent potential therapeutic targets.
Another factor explaining the osteotropism of CSCs is their ability to recognize chemokine gradients toward BM, through the CXCL12-CXCR4 axis, also known to be involved in tumor metastasis to other organs.
CXCR4 was more expressed in PT than in metastases (p = 0.0067), whereas CXCL12 was highly expressed in metastatic lesions located in liver and lung (p < 0.0001), as reported for human breast cancer.
CXCL12 is deeply involved in the process of tumor metastasis and T-cell homing, which is driven by a chemokine gradient, but healthy bones are supposed to preferentially express CXCL12.
Although this study will need further in vivo validation, our observations suggest that (a) silencing of CXCL12 in cervical cancer cells may be critical in migration and invasion, the key events in cancer cell metastases; (b) cervical cancer cells having down regulated CXCL12 are more prone to being attracted to CXCL12 expressed at secondary sites of metastases; and (c) CXCL12 inhibits anchorage independent cell growth via anoikis.
Therefore, blocking the interaction between CXCR4 and SDF-1 could alter the tumor's metastatic phenotype and control the development and progression of cancers.
Here, we show that stromal cell-derived factor-1 (SDF-1/CXCL12) is highly expressed in active MM, as well as in BM sites of tumor metastasis and report on the discovery of the high-affinity anti-SDF-1 PEGylated mirror-image l-oligonucleotide (olaptesed-pegol).
Recently, the CXCL12/CXCR4 axis has emerged as a key mediator of tumor metastasis; therefore, the possibility that identification of CXCR4 inhibitors can be a promising strategy for abrogating metastasis has been considered.
Physiological gradient formation within the device facilitated interrogation of key differences in chemotaxis among CXCL12 isoforms and suggests CXCL12-γ as a biomarker for metastatic cancer.
Given the demonstrated importance of CXCL12/SDF-1 in angiogenesis and tumour metastasis, we hypothesized that CXCR7 may also play a role in tumour pathogenesis.
Association between SDF1-3'A or CXCR4 gene polymorphisms with predisposition to and clinicopathological characteristics of prostate cancer with or without metastases.
These data indicate that CXCR4-CXCL12 axis and its cross-talking with VEGF plays a role in uveal melanoma metastases and may be new prognostic markers in UMM.
An exception is the angiogenic ELR(-)CXC chemokine stromal cell-derived factor-1 (CXCL12/SDF-1), which binds to CXCR4 and CXCR7 and is implicated in tumor metastasis.
The ability of Kp-10 to inhibit signaling and chemotaxis induced by SDF-1 indicates that activation of GPR54 signaling may negatively regulate the role of CXCR4 in programming tumor metastasis.