Lung-Seeking Metastases.

Giulia M Stella,Chandra Bortolotto,Silvia Benvenuti,Stefan Kolling

doi:10.3390/cancers11071010

Abstract

Metastases from different cancer types most often affect the lung parenchyma. Moreover, the lungs are among the most frequent sites of growth of metastatic masses of uncertain/unknown lineage of origin. Thus, with regards to pulmonary neoplastic parenchymal nodules, the critical issue is to determine if they are IN the lung or OF the lung. In this review, we highlight the clinical, instrumental and molecular features which characterize lung metastases, mainly focusing on recently advancing and emerging concepts regarding the metastatic niche, inflammation, angiogenesis, immune modulation and gene expression. A novel issue is related to the analysis of biomechanical forces which cooperate in the expansion of tumor masses in the lungs. We here aim to analyze the biological, genetic and pathological features of metastatic lesions to the lungs, here referred to as site of metastatic growth. This point should be a crucial part of the algorithm for a proper diagnostic and therapeutic approach in the era of personalized medicine.

Highlights

Metastatic dissemination is a feature of highly malignant progression which is responsible for poor prognosis of affected patients and eventually leads to their death
cancer of unknown primary (CUP) are properly defined as which is represented by adenocarcinomas (90%), with squamous cell carcinomas and undifferentiated carcinomas, the vast majority of which is represented by adenocarcinomas (90%), with squamous cell carcinomas being considerably less frequent
The vast majority of circulating tumor cells may possess intrinsic defects that preclude them from surviving or undergoing active proliferation in the lung, the ones that are fated to give rise to clinical metastases, the metastasis-initiating cells, feature a stem-cell like phenotype and face strong antimetastatic signals originating from the parenchyma of this organ [65]

Summary

Introduction

Metastatic dissemination is a feature of highly malignant progression which is responsible for poor prognosis of affected patients and eventually leads to their death. The application of phylogenetic analysis to cancer metastatic subclones could be helpful in dissecting evolutionary history of cancer lineages [3]. The latter could lead to the identification of driver genetic lesions that will impact on clinical management of advanced disease. The lungs are the second most frequent site of metastatic growth from extra-thoracic malignancies, with pulmonary secondary lesions being detected in 20–54% of cases [4]. They result from both lymphatic and hematogenous spread. We discuss and analyze the clinical, radiological and specific molecular features of secondary pulmonary masses as well as point out the biological and biomechanical properties of the lungs as sites of metastatic seeding

Clinical and Radiological Presentation of Pulmonary Metastases

The Pulmonary Metastatic Niche and Microenvironment

Genetic Signature Associated to Metastatic Tropism to the Lungs

Mechanical Interactions between Tumor Masses and Surrounding Microenvironment

Findings

Concluding Remarks