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The role of nervous system in progression of breast cancer: focusing on neuropeptides released from sensory neurons and inflammatory mediators

Objective

Breast cancer is the leading cause dead in women. Mortality arises from distant metastases. Hence it is crucial to reveal host and tumour derived factors responsible from metastasis. Recently I have found that sensory neurons sensitive to capsaicin are important in cancer progression. Specifically, inactivation of sensory neurons with capsaicin increased lung metastases significantly.

This is probably due to both altered tumour microenvironment and systemic response to tumour. Sensory nerves contain vasoactive peptides such as Substance P (SP) and Vasoactive Intestinal Peptide (VIP). In order to understand the mechanisms, I have screened expression of 12000 genes in primary breast carcinomas (4T1 cell line) from control and capsaicin treated animals (Balb-c mice). I found that inactivation of sensory neurons allows growth of cancer cells with higher metastatic potential and that decreased expression of peptidases and substance P fragments may increase breast cancer metastases (manuscript in preparation).

Definitive proofs however are missing. Hence my first goal is to clarify the role of neuropeptides and their physiological fragments in breast cancer progression. Specifically I will treat the balb-c mice injected with 4T1 cells with SP fragments that were identified in my previous work and will determine their possible anti-tumour effects. Sensory neuromediators regulates immune system, such that while some induces inflammatory response, others stimulate anti-inflammatory pathways. Chronic inflammation is a significant risk factor for development of malignancy. Since inactivation of sensory neurons enhanced the metastases, it is likely that uncontrolled inflammation occurred following inactivation. To clarify this point inflammatory and anti-inflammatory cytokines as well as the levels of neuropeptides involved in immune regulation (SP and VIP) will be examined.

Call for proposal

FP6-2004-MOBILITY-12
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Funding Scheme

IRG - Marie Curie actions-International re-integration grants

Coordinator

AKDENIZ UNIVERSITY, SCHOOL OF MEDICINE
Address
Dumlupinar Boulevard, Campus
Antalya
Turkey