Abstract
Metastasis is responsible for most of the cancer-associated deaths and proceeds through multiple steps. Several lines of evidence have established an indispensable involvement of macrophages present at the primary tumor sites in various steps of metastasis, from primary tumor growth to its intravasation into circulation. The lungs encompass a large, dense vascular area and, therefore, are vulnerable to metastasis, particularly, hematogenous ones arising from various types of neoplasms. Lung tissues constitutively contain several types of tissue-resident macrophages and circulating monocytes to counteract potentially harmful exogenous materials, which directly reach through the airway. Recent advances have provided an insight into the ontogenetic, phenotypic, and functional heterogeneity of these lung macrophage and monocyte populations, under resting and inflammatory conditions. In this review, we discuss the ontogeny, trafficking dynamics, and functions of these pulmonary macrophages and monocytes and their potential roles in lung metastasis and measures to combat lung metastasis by targeting these populations.
Highlights
Metastatic lesions are presumed to be responsible for nearly 90% of cancer-associated deaths [1].Metastasis is defined as the dissemination of cancer cells from the primary tumor site to distant organs, resulting in the formation of secondary tumor tissues [1,2]
Cancer cells at metastasis sites might more efficiently induce innate and acquired immune response, but this response might be counteracted by tumor-associated macrophages (TAMs), macrophages present at tumor sites, with a potential capacity to exert immune suppressive activities in most cases [4]
Parallel progression model is supported by observations in mouse models, where cancer cells disseminated at an early time point without appreciable primary tumor formation [5,6,7]
Summary
Metastatic lesions are presumed to be responsible for nearly 90% of cancer-associated deaths [1]. Monocytes can be classified into two subsets, classical (inflammatory) and patrolling monocytes, and lung tissue-resident macrophages consist of two distinct populations, alveolar macrophages (AMs) and interstitial macrophages (IMs) These cell populations can be discriminated based on the expression patterns of cell surface markers (Table 1) [11,12]. These cells sometimes polarize into so-called tip-dendritic cells (DCs) with a capacity to present antigen and express tumor necrosis factor (TNF)-α and NO synthase [14] These classical monocytes move to perivascular areas of tumor tissues to become so-called metastasis-associated macrophages (MAMs) with characteristic. All tissue-resident macrophages were presumed to arise from circulating bone marrow-derived monocytes [26] This hypothesis was challenged by a seminal study which identified yolk sac as another source of macrophages which is active before definitive hematopoiesis begins in the fetal liver [27].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
