“Scar-cinoma”: viewing the fibrotic lung mesenchymal cell in the context of cancer biology

Abstract

Lung cancer and pulmonary fibrosis are common, yet distinct, pathological processes that represent urgent unmet medical needs. Striking clinical and mechanistic parallels exist between these distinct disease entities. The goal of this article is to examine lung fibrosis from the perspective of cancer-associated phenotypic hallmarks, to discuss areas of mechanistic overlap and distinction, and to highlight profibrotic mechanisms that contribute to carcinogenesis. Ultimately, we speculate that such comparisons might identify opportunities to leverage our current understanding of the pathobiology of each disease process in order to advance novel therapeutic approaches for both. We anticipate that such “outside the box” concepts could be translated to a more precise and individualised approach to fibrotic diseases of the lung.

Pulmonary scar carcinoma in South Africa

“…[11] Studies evaluating fibrotic biopsies from patients with idiopathic pulmonary fibrosis (IPF) have shown a paucity of apoptosis, similar to that of malignancies, which may indicate a synonymous ability of both fibrotic and malignant tissue to evade cell death. [2,10] A possible explanation for this lack of apoptosis could be explained by overexpression of anti-apoptotic protein kinases, such as survivin. [12] Furthermore, the process of autophagy, by which cell death occurs via the lysosomal pathway, has been shown to be impaired in IPF as well as fibroblast models.…”

“…[1] The presence of dense hyaline scarring in the centre of many primary peripheral lung carcinomas led to recognition of the phenomenon of a lung scar carcinoma, although it was not clear whether the relevant area of scarring preceded the carcinoma or was caused by the carcinoma. [1,2] In recent years there has been renewed interest in scar carcinomas, also referred to as 'scar-cinomas' . [2] It has been reported that the presence of large numbers of fibroblasts and myofibroblasts is a hallmark of carcinomas.…”

“…[1,2] In recent years there has been renewed interest in scar carcinomas, also referred to as 'scar-cinomas' . [2] It has been reported that the presence of large numbers of fibroblasts and myofibroblasts is a hallmark of carcinomas. [3] Moreover, malignant cells hijack the host wound-repair response to promote formation of the tumour stroma, which is fundamental for cancer progression.…”

“…Impaired autophagy is a commonly accepted mechanism of tumourigenesis. [2] Sustained proliferative signalling is also considered to be a hallmark of tumourigenesis, in which sustained exogenous stimuli 'hijack' the cell cycle. [13] This overexpression of proliferative signalling networks has been shown also to be present in fibroblasts from IPF biopsies.…”

“…[3] The persistence of activated mesenchymal cells is therefore critical to the pathobiology of both fibrosis and cancer. [2,3] The Western Cape Province of South Africa (SA) has one of the highest recorded incidences of pulmonary tuberculosis (TB) in the world, and also carries a high burden of smoking-related diseases including lung cancer. [4] However, the potential association between pulmonary scarring and lung cancer has never been described in the local population.…”