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Table 1 A summary of Neurotensin (NT) and its receptors research studies

From: The role of Neurotensin and its receptors in non-gastrointestinal cancers: a review

Site of cancer

In-vitro

Animal models

Prognostic/Predictive studies

Clinical trials

Lung (NSCLC)

Treatment with NT increased growth in LMN-R cells

NTSR1 blockade potentiates effect of geftinib

NTSR3 good prognostic marker

Afatinib in stage IV bronchial adenocarcinoma

NTSR1 in cytoplasm a.w. poor prognosis

NTSR1 predicts worse sensitivity to platinum based treatments

NTSR2 expression has no correlation to OS

Pleural mesothelioma

NTSR1 antagonist reduced cell invasion in MSTO-211H cells

 

High NT expression is an independent predictor of poor 5-year survival

 

NTSR1 had no impact of survival

Pancreas

NTSR1 promotes DNA synthesis, proliferation, angiogenesis

 

NTSR1 increases with stage of disease

NI

NTSR3 increases migration in individually migrating PDAC cells

Breast

 

NTSR1 antagonist arrested tumour growth in xenografted MDA-MB-231 cells

High NTSR1 in patients with IDCs correlated to higher histoprognostic grade, larger tumour size and higher number of positive lymph nodes

NI

Suicide HSVtk gene delivery by NT-polyplex nanoparticles + ganciclovir to treat MDA-MB-231 cells

High NTSR1 expression is associated with worse survival

Prostate

NT/NTSR1 in PC3 cells stimulates EGFR/ERK/Akt phosphorylation and DNA synthesis which is PKC-dependent

(64) Cu chelators conjugated to a NT analog was assessed as an imaging marker using PET/CT to was correlated to NTSR1-positive lesions

Use of Lu-177-labelled NTSR1 antagonists in PSMA negative and NTSR1 positive prostate cancer nude mice showed reduced tumour growth over 57 days

There is more frequent NTSR1 overexpression in metastatic lymph nodes compared to primary tumours

 

NTSR1 is found in poorly differentiated (androgen receptor negative)

NTSR2 was found in well-differentiated cell lines

NTSR3 found in all cell lines

HNSCC

Addition of NT promoted invasion and migration.

Knockdown of NTSR1 slowed invasion and migration

NI

High mRNA expression of NT and NTSR1 has a worse metastasis-free survival rate

NI

Glioma

Glioblastoma multiforme (GBM)

NT stimulates ERK1/2 phosphorylation

NTSR1 blockade in xenografted nude mice increased survival

NI

NI

Different GBM cell lines express different NT receptors

NI

NI

NI

Studies on glioblastoma stem cells show that NT acts through the CXCR1/2/IL-8 pathway which is EGFR-dependent

   
  1. CXCR CXC chemokine receptor, EGFR epidermal growth factor receptor, ERK extracellular signal-regulated kinase, IDC invasive ductal carcinoma (breast), IL-8 interleukin 8, MDA-MB-231 triple negative breast cancer cells, NTSR neurotensin receptor, NI not investigated, OS overall survival, PC3 cell line from bone metastasis of prostate cancer patient, PDAC pancreatic ductal adenocarcinoma cells, PKC protein kinase C, PSMA prostate specific antigen