Differential Expressions of Matrix Metalloproteinases, A Disintegrin and Metalloproteinases, and a Disintegrin and Metalloproteinases with Thrombospondin Motifs and their Endogenous Inhibitors Among Histologic Subtypes of Lung Cancers

Lung cancer is a heterogeneous disease with several histologic subtypes. The two major pathologies, which account for approximately 70% of lung cancers, are adenocarcinoma (AD) and squamous cell carcinoma (SQ). Traditionally, these two subtypes have been categorized as non-small-cell lung cancer and treated similarly. However, they are different not only pathologically, but also functionally. For example, F-18-fluorodeoxyglucose positron emission tomography (FDG-PET), which assesses glucose metabolism in tumor tissues, shows that SQ has higher glucose metabolism than does AD. Matrix metalloproteinases (MMPs) and their inhibitors play pleiotropic roles in cancer development, carcinogenesis, apoptosis, angiogenesis, invasion and metastasis. Expression of MMPs and their associated molecules is different among the subtypes of lung cancer. Expression levels of MMP-2, MMP-7, reversion-inducing cysteine-rich protein with Kazal motifs (RECK), tissue inhibitors of metalloproteinase (TIMP)-1, and TIMP-2 are higher in AD than in SQ. In contrast, expression levels of MMP-1, MMP-8, MMP-9 and TIMP-3 are higher in SQ than in AD. Serum levels of a disintegrin and metalloproteinase (ADAM)-8 and ADAM-28 are higher in lung cancer patients than in healthy controls. High expression of ADAM-28 correlates with metastasis and recurrence, but there is no significant difference in ADAM-8 or ADAM-28 expression between AD and SQ. It is necessary to recognize the differential expression patterns of MMPs, their endogenous inhibitors and associated molecules for each subtype of lung cancer in order to develop clinical markers, therapeutic inhibitors and treatment strategies using MMP inhibitors.