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CXCL12-CXCR4 axis promotes the natural selection of breast cancer cell metastasis
- Source :
- Tumour Biology
- Publisher :
- Springer Nature
-
Abstract
- CXCR4 and its ligand CXCL12 can promote the proliferation, survival, and invasion of cancer cells. They have been shown to play an important role in regulating metastasis of breast cancer to specific organs. High CXCR4 expression was also correlated to poor clinical outcome. Previous study also showed that tumor cells express a high level of CXCR4 and that tumor metastasis target tissues (lung, liver, and bone) express high levels of the ligand CXCL12, allowing tumor cells to directionally migrate to target organs via a CXCL12-CXCR4 chemotactic gradient. However, the exact mechanisms of how CXCR4 and CXCL12 enhance metastasis and/or tumor growth and their full implications on breast cancer progression are unknown. Yet it is likely that chemokine receptor signaling may provide more than just a migrational advantage by also helping the metastasized cells establish and survive in secondary environments. In this study, we investigated CXCR4 and CXCL12 expression in breast cancer and analyzed its association with clinicopathological factors by immunohistochemistry first. Then, we detected the mRNA and protein expression of CXCR4 and CXCL12 in breast cancer cell lines by Western blot and RT-PCR. The MDA-MB-231 has CXCR4 expression and very weak CXCL12 expression. So, we constructed the functional CXCL12 expression in MDA-MB-231 using a gene transfection technique. Further experiments were conducted to evaluate the effect of CXCL12 transfection on the biological behaviors of MDA-MB-231. The cell proliferation of MDA-MB-231–CXCL12 was accessed by MTT assay; the apoptosis was analyzed by an AnnexinV-FITC/propidium iodide double staining of flow cytometry method; and the cell invasive ability was examined by Matrigel invasion assay. Immunohistochemical analysis showed the co-expression of CXCR4 and CXCL12 correlated with lymph node metastasis and TNM stage (p
- Subjects :
- Adult
Receptors, CXCR4
Cancer Research
Cell
Apoptosis
Breast Neoplasms
Biology
Transfection
CXCR4
Metastasis
Chemokine receptor
Breast cancer
Cell Line, Tumor
medicine
Humans
Neoplasm Invasiveness
Neoplasm Metastasis
Aged
Cell growth
General Medicine
Middle Aged
CXCL12
medicine.disease
Immunohistochemistry
Chemokine CXCL12
biological factors
medicine.anatomical_structure
Cancer cell
embryonic structures
Cancer research
Female
biological phenomena, cell phenomena, and immunity
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 10104283
- Volume :
- 35
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Tumor Biology
- Accession number :
- edsair.doi.dedup.....3eaae01d4bc587a055d437d610bdfca7
- Full Text :
- https://doi.org/10.1007/s13277-014-1816-1