The diffuse endocrine system: from embryogenesis to carcinogenesis

Abstract

In the present review we will summarise the current knowledge about the cells comprising the Diffuse Endocrine System (DES) in mammalian organs. We will describe the morphological, histochemical and functional traits of these cells in three major systems gastrointestinal, respiratory and prostatic. We will also focus on some aspects of their ontogeny and differentiation, as well as to their relevance in carcinogenesis, especially in neuroendocrine tumors. The first chapter describes the characteristics of DES cells and some of their specific biological and biochemical traits. The second chapter deals with DES in the gastrointestinal organs, with special reference to the new data on the differentiation mechanisms that leads to the appearance of endocrine cells from an undifferentiated stem cell. The third chapter is devoted to DES of the respiratory system and some aspects of its biological role, both, during development and adulthood. Neuroendocrine hyperplasia and neuroendocrine lung tumors are also addressed. Finally, the last chapter deals with the prostatic DES, discussing its probable functional role and its relevance in hormone-resistant prostatic carcinomas.

Prostate Cancer and Neuroendocrine Differentiation: More Neuronal, Less Endocrine?

“…NE cells display a combination of neuronal and endocrine features, best described as a partly neuron-like morphology and an endocrine-like secretory mechanism (see below). The whole NE concept itself had nothing to do with cancer; it arose in the late 1920s, when it was discovered that some hypothalamic neurons secrete their products into the bloodstream rather than into a specialized synaptic cleft as well described by Montuenga and colleagues (2). Subsequently, the existence of hybrid, neuronal-endocrine cell type, NE, was widely accepted.…”

“…Yet, they also can be found within endocrine glands or tissues, such as the hypothalamus, anterior pituitary, pineal gland, thyroid gland (calcitonin-secreting cells), thymus, breast, and the pancreatic islets of Langerhans [reviewed in Ref. (2–4)]. For terminology clarification, we note that usually the term “NE” refers to both cancerous and non-cancer-related cells, while the term “NED” (with a “D”) refers specifically to cancerous cells.…”

Upregulation of manganese superoxide dismutase (SOD2) is a common pathway for neuroendocrine differentiation in prostate cancer cells

“…NE cells, included in the diffuse endocrine system, share common features with neurons and are present at all the stages from normal benign to prostate adenocarcinomas. 3 They are thought to exert regulatory functions through the production of several substances, 5 although their exact role has not been elucidated yet. A large heterogeneity in NE cells, suggesting the presence of several populations with different functions has been proposed.…”

Diffuse Endocrine System, Neuroendocrine Tumors and Immunity: What’s New?

“…The diffuse endocrine system (DES) is composed of neuroendocrine cells scattered throughout the entire body, either isolated or grouped to form discrete aggregates, such as the neuroepithelial bodies in the bronchopulmonary tract or the islets of Langerhans in the pancreas [1]. While at least some of the DES cells in the gut are known to regulate secretion, absorption, motility, and mucosal proliferation [2], the physiological role of the neuroendocrine cells in most other organs remains elusive.…”