Histogenesis of colon cancer in experimental animals.
Following the introduction of colon-specific carcinogens, the mode of formation and evolution of colon cancer has been investigated in experimental animals. These carcinogens are cytotoxic to epithelial cells in colonic crypts and induce a series of non-specific acute and chronic changes including cryptal hyperplasia when administered repeatedly. During such processes, a number of neoplastically transformed cells may appear in many crypts. Only when they occur at the base of or form an outpocketing pouch in a crypt, do they appear to succeed in repopulating the given crypt to form a dysplastic crypt, from which an early neoplastic lesion develops usually in the upper part of the mucosa. The neoplastic lesion thus formed grows by various mechanisms, depending on its intrinsic properties of unceasing proliferative activity of neoplastic cells and interaction with the microenvironment: (a) by elongation and tortuosity of neoplastic glands, (b) by evagination of the glandular epithelial lining, with the formation of septa to dichotomise the glands to increase the number of neoplastic glands or with formation of incomplete septa or villi to expand the surface area of the neoplasm, and (c) by invagination and outpocketing pouch formation of neoplastic glands when accompanied with the changes in the basement membrane. In doing so, it may progress in various directions to form a polypoid or discoid lesion. Concomitant with growth, the neoplastic cells may undergo a series of cytological alterations and penetrate through their basement membrane in some areas to manifest early malignant behaviour. With downward progression, the neoplasm penetrates the muscularis mucosae and invades the submucosa, muscularis externa and serosa. Such an invasive process is often associated with the rearrangement of fibroblasts, marked changes in the production of collagen and proteoglycans of the extracellular matrix and lysis of the existing structures of the colonic wall. On morphological grounds, colonic carcinogenesis is a multiple process and is associated with successive breakdown of the host defence barriers. From the studies on experimental colonic tumourigenesis, adenomas and adenocarcinomas appear to share a common aetiological factor, or factors, and they are different end-stages in the evolution of neoplastically transformed cells. At any stage of evolution, however, benign neoplasms may develop dysplastic foci within neoplasms and evolve into a malignant form.
D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology; D000236:Adenoma / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D001485:Basement Membrane / Q000473:pathology; D002273:Carcinogens; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000473:pathology; D003106:Colon / Q000473:pathology*; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000473:pathology; D007413:Intestinal Mucosa / Q000473:pathology; D051379:Mice; D008871:Microvilli / Q000473:pathology; D009361:Neoplasm Invasiveness; D051381:Rats
D002273:Carcinogens