Multifocal epithelial tumors and field cancerization: stroma as a primary determinant

Abstract

It is increasingly evident that cancer results from altered organ homeostasis rather than from deregulated control of single cells or groups of cells. This applies especially to epithelial cancer, the most common form of human solid tumors and a major cause of cancer lethality. In the vast majority of cases, in situ epithelial cancer lesions do not progress into malignancy, even if they harbor many of the genetic changes found in invasive and metastatic tumors. While changes in tumor stroma are frequently viewed as secondary to changes in the epithelium, recent evidence indicates that they can play a primary role in both cancer progression and initiation. These processes may explain the phenomenon of field cancerization, i.e., the occurrence of multifocal and recurrent epithelial tumors that are preceded by and associated with widespread changes of surrounding tissue or organ "fields."

Sexual dimorphism in cancer

“…1). An important notion is that cancer as a disease is not limited to a group of genetically deranged cells and their immediate environment, but is linked to general alterations in organ homeostasis as a result of perturbed developmental/morphogenetic signals and systemic factors 43,159 . Selection of cells with cumulative somatic mutations 160 or a "Big Bang" expansion of single cell populations with pre-existing dominant alterations 161 have been implicated in cancer development.…”

“…By contrast, the role that these pathways play in self-renewal of initiating cancer cells of other types is a mostly unexplored topic and important area of future investigation. b) Cancer stroma : The tumor microenvironment plays a crucial role in both initiation and progression of the disease 43,44 . Various components of the stromal compartment are under sex hormone control.…”

“…c) Inflammatory/immune system : The microenvironment encompasses different leukocyte populations, with macrophage M1 polarization playing a key role in chronic inflammation-associated cancer development 43 . In macrophages, ERα significantly reduces their pro-inflammatory activity 58 and tumor promoting properties 59 .…”

WITHDRAWN: Lack of miR-216b-5p, miR-33a-5p or miR-122-5p in MSCs exosomes promotes breast cancer glycolysis by targeting HK2, LDHA and PKM2

“…It is verified that bone marrow MSCs is the main source of carcinoma associated fibroblasts in breast cancer microenvironment [3]. Breast cancer is the most common cancer from women and the role of tumor microenvironment in breast cancer progression is studied widely, but the relationship between MSCs and breast cancer cells is still unclear [4].…”

CSL-p53: From senescence to CAF activation

“…The events governing this process are not fully understood, but most likely a tumor-permissive microenvironment is required. 5 Stromal changes associated with cell senescence are thought to play an important role in the increased incidence of age-related cancers. 6 However, this process may be more relevant in the initial phase of cancer development rather than at an advanced stage, the latter being characterized by increased fibroblast density and proliferation.…”