Nature Reviews Cancer has an interesting opinion piece on tumor microenvironments, and how addressing cancer therapy as a problem of chronic inflamation may be an effective therapeutic framework for limiting tumor growth. Albini and Sporn provide the following insights, shown schematically in Figure 1:
There is a discrete order of events in physiologically acute inflammation and repair10 (Fig. 1a). However, these events become chaotically disorganized during chronic unresolved inflammation and carcinogenesis (Fig. 1b). This chaotic local microenvironment has led to the suggestion that tumours are ‘wounds that do not heal’11. The constant disruption of homeostasis by proliferating epithelial cells produces a chronic inflammatory reaction, which is an abortive attempt to re-establish homeostasis through tissue remodelling12. However, the classic players in acute inflammation (granulocytes, macrophages, endothelial cells and fibroblasts) that ordinarily lead to the resolution of a wound through an orderly series of events, instead react paradoxically to the presence of dysfunctional epithelial cells by promoting their survival and replication12. This process includes inflammatory angiogenesis.
What caught my attention was treating angiogenesis, as opposed to metastasis, according to the “seed and soil” hypothesis. In that view, angiogenesis is seen as a tissue-stromal response (extrinsic to the tumor), instead of as a response intrinsic to the tumor cells. Further, the authors argue that the normal tissue response can be described as an out-of-control inflammatory response.
Certainly, there’s an element of truth in that – endothelial cells and the tissue stroma need to cooperate with the tumor to facilitate angiogenesis. I think that Albini and Sporn are leaving out the role of hypoxic response factors in promoting angiogenesis, however.
Also interesting is the power of viewing cancer as *insert normal biologic process here* gone bad. We hear a lot about the stem cell theory of cancer, and indeed stem cells and cancer cells share a number of common features, particularly that of self-renewal and survival. There’s a similar value for viewing cancer cells as aberrant neural crest cells or lymphocytes attracted by some attractant cue, as the cancer cells move between tissues. And here, we have a common trait being exploited by innovative researchers, between the inflammatory response and cancer cells.
- Albini A, Sporn MB. (2007) The tumour microenvironment as a target for chemoprevention. Nat Rev Cancer. 2007 Jan 12; [Epub ahead of print]. Pubmed
- (10) Kumar, V., Abbas, A. K. & Fausto, N. Robbins and Cotran Pathologic Basis of Disease, 7th Edition 47–118 (Elsevier Saunders, Philadelphia, 2005).
- (11) Dvorak HF. Angiogenesis: update (2005). J. Thromb. Haemost. 3, 1835–1842. Pubmed
- (12) Albini A, Tosetti F, Benelli R, Noonan DM. (2005) Tumor inflammatory angiogenesis and its chemoprevention. Cancer Res. 65, 10637–10641. PUbmed