Somatostatin and CXCR4 expression patterns in adenocarcinoma and squamous cell carcinoma of the lung relative to small cell lung cancer

J Cancer Res Clin Oncol. 2018 Oct;144(10):1921-1932. doi: 10.1007/s00432-018-2722-5. Epub 2018 Aug 3.

Abstract

Purpose: Lung cancer is highly prevalent and has an especially poor prognosis. Thus, new diagnostic and therapeutic targets are necessary. Two potential targets are somatostatin receptors (SST), which are overexpressed in well-differentiated neuroendocrine neoplasms, and the chemokine receptor CXCR4, which is present mainly in highly proliferative and advanced tumours. Although their expression is relatively well characterized in small cell lung cancer (SCLC), in non-small cell lung cancer (NSCLC), data on SST and CXCR4 expression are scarce and contradictory.

Methods: We comparatively evaluated 83 tumour samples from a total of 57 lung cancer patients, of which 22 had adenocarcinoma (ADC), 21 had squamous cell carcinoma (SQC), and 15 had SCLC. Samples were evaluated for SST and CXCR4 expression using immunohistochemistry with well-characterized rabbit monoclonal antibodies.

Results: In the samples investigated, the most prominently expressed receptors were CXCR4 and SST5. Specifically, CXCR4 was detected with high expression intensity in more than 60% of ADC samples, about 90% of SQC, and 100% of SCLC. SST5 was present in about 75% of ADC and SQC samples and in more than 90% of SCLC. Although not noticeably expressed in ADC and SQC samples, SST2 was detected in 50% of SCLC cases, with a subset of patients displaying exceptionally high expression. The comparison of the three tumour entities revealed that SCLC samples had higher SST2, SST5, and CXCR4 expression, but lower SST3 and SST1 relative to ADC or SQC samples.

Conclusion: CXCR4 may be a promising target for diagnostics and therapy in both SCLC and NSCLC.

Keywords: CXCR4; Chemokine receptor; Non-small cell lung cancer; Small cell lung cancer; Somatostatin receptors.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / surgery
  • Female
  • Follow-Up Studies
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Prognosis
  • Receptors, CXCR4 / metabolism*
  • Signal Transduction
  • Small Cell Lung Carcinoma / metabolism*
  • Small Cell Lung Carcinoma / pathology
  • Small Cell Lung Carcinoma / surgery
  • Somatostatin / metabolism*
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • CXCR4 protein, human
  • Receptors, CXCR4
  • Somatostatin