Cancer as an overhealing wound: an old hypothesis revisited

Abstract

What is the relationship between the wound-healing process and the development of cancer? Malignant tumours often develop at sites of chronic injury, and tissue injury has an important role in the pathogenesis of malignant disease, with chronic inflammation being the most important risk factor. The development and functional characterization of genetically modified mice that lack or overexpress genes that are involved in repair, combined with gene-expression analysis in wounds and tumours, have highlighted remarkable similarities between wound repair and cancer. However, a few crucial differences were also observed, which could account for the altered metabolism, impaired differentiation capacity and invasive growth of malignant tumours.

Human liver flukes

“…Re-infection, which is common and often continual in endemic areas, results in more severe inflammation, and accelerated fibrosis (39) . Induction of fibrosis after inflammation is an important part of the pathway of pathological changes that lead to cholangiocarcinoma (40) . These abnormalities do not occur in all patients, with a subset producing a stronger inflammatory response and then faster and more advanced periportal fibrosis deposition, predisposing them to cholangiocarcinoma (36) .…”

Monocytes and Macrophages in Cancer: Development and Functions

“…Under steady-state conditions, macrophages support either homeostatic processes or trophic processes for tissue development/remodeling in developing or healing tissues [4,5]. The mechanisms involved in this support include phagocytosis, growth factor production, angiogenesis and degradation of ECM components by secreted MMPs (matrix metallo-proteinases) [4,5]. In response to immunogenic signals (such as Toll-like receptor (TLR) signals or inflammatory cytokines), the functional properties of macrophages are polarized towards processes needed for immunity and pathogen defense.…”

“…They colonize every organ in the body and, based on the location, some specialized macrophages have received specific names, e.g., Kupffer cells in the liver, microglia in the neuronal tissue and osteoclasts in the bone. They have specific functions under tissue homeostasis including phagocytosis of apoptotic cells, growth factor production and angiogenesis induction [4,5]. In response to inflammation, they are needed for pathogen clearance, followed by a phase of tissue repair and wound healing that promotes restoration of homeostasis [5].…”

“…They have specific functions under tissue homeostasis including phagocytosis of apoptotic cells, growth factor production and angiogenesis induction [4,5]. In response to inflammation, they are needed for pathogen clearance, followed by a phase of tissue repair and wound healing that promotes restoration of homeostasis [5]. Monocytes are precursors of resident macrophages.…”

A Novel Enhancer of the Wound Healing Process

“…1 A particularly important component of the wound granulation tissue and the tumor stroma is the vasculature, which is essential for supplying the wound or tumor tissue with oxygen and nutrients. Thus, impaired angiogenesis is a hallmark of chronic, nonhealing ulcers, and stimulation of angiogenesis at the wound site is a promising treatment strategy.…”