J Lung Cancer.  2011 Dec;10(2):69-76. 10.6058/jlc.2011.10.2.69.

Somatostatin Receptors in Lung Cancer: From Function to Molecular Imaging and Therapeutics

• Callison J
• Walker RC
• Massion PP

• KMID: 2005737
• DOI: http://doi.org/10.6058/jlc.2011.10.2.69

Abstract

Lung cancer is a deadly disease that is difficult to diagnose and even more difficult to treat effectively. Many pathways are known to affect tumor growth, and targeting these pathways provides the cornerstone by which cancer is treated. Somatostatin receptors (SSTR) are a family of G protein coupled receptors that signal to alter hormonal secretion, increase apoptosis, and decrease cellular proliferation. These receptors are expressed in many normal and malignant cells, including both small cell and non-small cell lung cancer. Synthetic analogs of SSTRs are commercially available, but their effects in lung cancer are still largely uncertain. Signaling pathway studies have shown that SSTRs signal through phosphotyrosine phosphatases to induce apoptosis as well as to decrease cell proliferation. Radiolabeled SSTR2 analogs are utilized for radiographic imaging of tumors, which, when combined with positron emission tomography-computed tomography (PET-CT) may improve detection of lung cancer. These radiolabeled SSTR2 analogs also hold promise for targeted chemotherapy as well as radiotherapy. In this review, we summarize what is known about SSTRs and focus our discussion on the knowledge as it relates to lung cancer biology, as well as discuss current and future uses of these receptors for imaging and therapy of lung cancer.

Keyword

Somatostatin receptors; Lung neoplasms; Neuroendocrine tumors; Molecular imaging

MeSH Terms

Apoptosis
Biology
Carcinoma, Non-Small-Cell Lung
Cell Proliferation
Electrons
Humans
Lung
Lung Neoplasms
Molecular Imaging
Neuroendocrine Tumors
Phosphoric Monoester Hydrolases
Phosphotyrosine
Receptors, G-Protein-Coupled
Receptors, Somatostatin
Somatostatin
Phosphoric Monoester Hydrolases
Phosphotyrosine
Receptors, G-Protein-Coupled
Receptors, Somatostatin
Somatostatin

Figure

• 

  Fig. 1. Somatostatin receptor sig-naling cascade. SSTR activation decreases hormonal secretion in most cells by decreasing cyclic AMP and by altering voltage gat-ed potassium and calcium cha-nnels. In a minority of cells (pan-creatic B-cells), hormonal secretion is increased. SSTR signals through PTPases to alter ERK1/2 phosphorylation to impair p27 kip1 degradation which leads to cell growth arrest. SSTR also signals through PTPases to induce apoptosis. Rarely SSTR2 induces proliferation. ERK: extracellular signal- regulated kinase, Gα, Gβ, Gγ: G- protein subunit, PLC: phospholi-apse C, cAMP: cyclic adenosine monophosphate, IP3: inositol tri-phosphate, PTPase: phosphotyrosine phosphatase, SRIF: somatostatin, SHP: Src homology phosphatase, PTP-η: phosphotyrosine phosphatase η.

• 

  Fig. 2. Use of a new synthetic somatostatin analog in lung cancer: Axial (A, B) and coronal (C, D) fused PET/CT images in a patient with newly diagnosed, un-treated adenocarcinoma of the right upper lobe (arrows). The tumor is easily seen with both the somatostatin analog (68 Ga-DOTATATE; A, C) and with conventional PET imaging (18 F-FDG: B, D) with com-parable uptake (each had an SUV value of 2.7). The combination of both imaging agents may help reduce false positive exams with 18 F-FDG PET/CT imaging alone, decreasing unnecessary biopsies or thoracotomies. Images by the authors.

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