CXCL12-binding receptors expression in non-small cell lung cancer relates to tumoral microvascular density and CXCR4 positive circulating tumoral cells in lung draining venous blood

Eur J Cardiothorac Surg. 2012 Feb;41(2):368-75. doi: 10.1016/j.ejcts.2011.05.009. Epub 2011 Dec 12.


Objectives: Lung cancer is the main cause of cancer-related death in Western countries. Despite early diagnosis, approximately 40% of patients have undergone surgical resection for localized non-small cell lung cancer relapse within 24 months after surgery. Current prognostic criteria for patients with non-small cell lung cancer are gradually enriched by the discovery of critical biological markers in surgical samples to better stratify patients with high risk for recurrent and metastatic disease after surgical manipulation. In fact, specific biological features are needed to drive metastasis development and, among these chemokine receptors, when activated, seem to play a relevant role, promoting both neovessels formation and tumoral cell migration.

Methods: To this purpose, blood samples from the closed stumps of the pulmonary veins were drawn immediately after major pulmonary surgery in 45 patients with resectable non-small cell lung cancer to evaluate the expression of chemokine CXCL12 receptor, CXCR4, in circulating tumor cells. In addition, primary tumor sections have been used to assess microvascular density (MVD) and vessels invasion and build prognostic tissue micro-array to investigate the expression of CXCL12 receptors CXCR4 and CXCR7.

Results: Cells positive for cytokeratins from tumor draining pulmonary venous blood were detectable in 11 cases (23.9%). In 8 out of 11 cases, CK positive cells coexpressed CXCR4. Moreover, in tumoral tissue high CXCR4 expression was significantly associated to high mMVD (p = 0.046), high CXCR7 expression (p = 0.001), adenocarcinoma histotype (p = 0.023), and to the presence of circulating tumoral cells in pulmonary veins (p = 0.001). Finally, vessel invasions relate to high MVD.

Conclusion: In conclusion, the results of our study underline the significant potential role of CXCL12 receptors in determining both vessel formation and tumoral cell migration to blood stream, favoring metastasis development.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Carcinoma, Non-Small-Cell Lung / blood supply
  • Carcinoma, Non-Small-Cell Lung / blood*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Chemokine CXCL12 / blood*
  • Epidemiologic Methods
  • Female
  • Humans
  • Keratins / metabolism
  • Lung Neoplasms / blood supply
  • Lung Neoplasms / blood*
  • Lung Neoplasms / pathology
  • Male
  • Microvessels / pathology
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Proteins / blood
  • Neoplasm Staging
  • Neoplastic Cells, Circulating / metabolism*
  • Prognosis
  • Receptors, CXCR / blood
  • Receptors, CXCR4 / blood*


  • ACKR3 protein, human
  • Biomarkers, Tumor
  • CXCL12 protein, human
  • CXCR4 protein, human
  • Chemokine CXCL12
  • Neoplasm Proteins
  • Receptors, CXCR
  • Receptors, CXCR4
  • Keratins