Human cholangiocarcinomas express somatostatin receptors and respond to somatostatin with growth inhibition

Abstract

BACKGROUND/AIMS: Cholangiocarcinoma, a malignancy of biliary epithelia, is usually fatal because of absence of tests for early detection and lack of effective therapy. Somatostatin (SS) receptors are expressed in several malignancies and in rodent biliary epithelia. We tested the hypothesis that SS receptors are present in cholangiocarcinomas.

METHODS: We examined tissue from seven surgically resected human cholangiocarcinomas and a human bile duct cancer cell line for the messenger RNA for one subtype of SS receptors (SSTR2) and studied binding and growth-active properties of SS and its analogues.

RESULTS: SSTR2 messenger RNA was expressed in all seven human cholangiocarcinoma specimens. Experiments with the human cholangiocarcinoma cell line showed specific, saturable binding of an SS analogue (MK-678) with high affinity for SSTR2 on cholangiocarcinoma membranes; inhibition in vitro of tumor cell proliferation by SS-14 and its analogue, octreotide; and inhibition in vivo of tumor growth in athymic mice implanted with human cholangiocarcinoma cells and treated with lanreotide, another SS analogue. Experiments to elucidate a possible mechanism of growth inhibition by SS showed it was not through changes in cellular cyclic adenosine monophosphate or calcium levels. Using gamma camera imaging with an 111In-SS analogue, we localized a histologically proven cholangiocarcinoma in a patient.

CONCLUSIONS: These results suggest that SS analogues may be useful for diagnostic localization and treatment of biliary tract malignancies.

 

About this publication.

See also:

- Official Web Site: The Di Bella Method;

- The Di Bella Method (A Fixed Part - Somatostatin, Octreotide, Sandostatin LAR, analogues and/or derivatives);

- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;

- Publication, 2018 Jul: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);

- Publication, 2018 Sep: The over-expression of GH/GHR in tumour tissues with respect to healthy ones confirms its oncogenic role and the consequent oncosuppressor role of its physiological inhibitor, somatostatin: a review of the literature (from Di Bella's Foundation);

- Publication, 2019 Aug: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes (from Di Bella's Foundation);

- The Di Bella Method (A Fixed Part - Bromocriptine and/or Cabergoline);

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

- The Di Bella Method (DBM) in the treatment of prostate cancer: a preliminary retrospective study of 16 patients and a review of the literature;

- Pancreatic Adenocarcinoma: clinical records on 17 patients treated with Di Bella's Method;

- The Di Bella Method Increases by the 30% the survival rate for Pancreas tumors and for this reason should be proposed as first line therapy for this type of cancer;

- Neuroblastoma: Complete objective response to biological treatment;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in advanced non-small-cell lung cancer patients with low performance status;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in chemotherapy-pretreated patients with advanced lung adenocarcinoma and low performance status;

- Observations on the Report of a case of pulmonary adenocarcinoma with lymph node, hepatic and osseus metastasis;

- The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma;

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide;

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck.