Complexity of Neural Component of Tumor Microenvironment in Prostate Cancer

Abstract

The tumor microenvironment (TME) plays an essential role in the development and progression of neoplasms. TME consists of the extracellular matrix and numerous specialized cells interacting with cancer cells by paracrine and autocrine mechanisms. Tumor axonogenesis and neoneurogenesis constitute a developing area of investigation. Prostate cancer (PC) is one of the most common malignancies in men worldwide. During the past years, more and more studies have shown that mechanisms leading to the development of PC are not confined only to the epithelial cancer cell, but also involve the tumor stroma. Different nerve types and neurotransmitters present within the TME are thought to be important factors in PC biology. Moreover, perineural invasion, which is a common way of PC spreading, in parallel creates the neural niche for malignant cells. Cancer neurobiology seems to have become a new discipline to explore the contribution of neoplastic cell interactions with the nervous system and the neural TME component, also to search for potential therapeutic targets in malignant tumors such as PC.

Association of Mu-Opioid Receptor(MOR) Expression and Opioids Requirement With Survival in Patients With Stage I-III Pancreatic Ductal Adenocarcinoma

“…Thus, we can speculate that MOR activation as the result of endogenous or exogenous opioids can trigger the release of soluble factors (i.e., nerve growth factor) that promote neurogenesis within the pancreatic cancer microenvironment (22). In our study, it is unlikely that a short period of exposure to sufentanil would trigger neurogenesis; therefore, we can speculate that elevated concentrations of locally released endorphins in patients with pain could be responsible of a high rate of neuritogenesis and perineural invasion (23). Alternatively, synthetic opioid such as fentanyl could promote neurotigenesis by regulating BNIP3 via miR-145-5 (24).…”

Investigation of Neural Microenvironment in Prostate Cancer in Context of Neural Density, Perineural Invasion, and Neuroendocrine Profile of Tumors

“…who showed that the co-culture of PCa cell line with dorsal root ganglion stimulated the outgrowth of neurites and the migration of tumor cells toward the neural structures ( 6 ). PCa represents a tumor with a specific microenvironment, where reciprocal interactions between nerves and other cellular and extracellular components were observed molecularly and clinically in vitro and in vivo ( 5 , 7 , 36 , 37 ). Neurotransmitters released within the tumor microenvironment modulate the expression of genes by targeting tumor receptors affecting the biological potential of cancer.…”

“…The neural stromal compartment is responsible for a specific microenvironment which is different in benign and malignant prostatic glands ( 5 ). The glandular part of the normal prostate is supplied by cholinergic fibers while the stromal part – by adrenergic ones and peptidergic nerve fibers.…”

Poly(ADP-Ribose) Polymerase Inhibitors in Prostate Cancer: Molecular Mechanisms, and Preclinical and Clinical Data

“…Recently, the relationship between cancer and the tumour microenvironment has become a new issue in prostate pathobiology [32]. PARP affects reciprocal interactions between cells in the tumour microenvironment, affecting prostate tumorigenesis and its aggressiveness [17,28,[33][34][35][36].…”