In favour of an oncofoetal concept of bronchogenic carcinoma development

Abstract

Our recent studies in a heterotopic model of non-small cell lung cancer in dogs (subcutaneous bronchial autografts treated with 3- ~i iethylchola~i threnhea) ve provided evidence that alveolar type I1 cells may newly arise during initial phases of bronchial carcino-genesis. In the light of these novel findings, which are in agreement with our observations in human non-small cell lung cancer, and in \~iew of present insighrs into embryonic lung differentiation, we discuss evidence that favours a new1. oncofoetal concept of bronchogenic carcinoma development. According to this concept, the primary cells of origin for these tilmors are undifferentiated primordial-like cells that derive from bronchial epithelial cells present in major bronchi or their divisions by retrodifferentiation. Such primordiallike cells of origin ~~nde rgnoo vel differentiation into the potential (alveolar, bronchial or primordial) tumor stem cells, which occupy the dividing cellular layers of the (pre)neoplastic lesions and constitute the actively dividing and invading part of the neoplasn~. Examples of tumors that may originate from alveolar tunlor stem cells are carcinon~aso f the bronchioloalveolar, papillary, acinar, and adenoid-cystic types. Squamous cell carcinon~asc ould possibly belong to this group as well, but much more evidence is required to reach conclusions regarding this type of cancer. We suggest that epithelial retrodifferentiation followed by novel differentiation (oncofoetal mechanism) is fundamental in bronchial carcinogenesis.