Site‐specific metastasis: A cooperation between cancer cells and the metastatic microenvironment

Abstract

The conclusion derived from the information provided in this review is that disseminating tumor cells (DTC) collaborate with the microenvironment of a future metastatic organ site in the establishment of organ‐specific metastasis. We review the basic principles of site‐specific metastasis and the contribution of the cross talk between DTC and the microenvironment of metastatic sites (metastatic microenvironment [MME]) to the establishment of the organ‐specific premetastatic niche; the targeted migration of DTC to the endothelium of the future organ‐specific metastasis; the transmigration of DTC to this site and the seeding and colonization of DTC in their future MME. We also discuss the role played by DTC‐MME interactions on tumor dormancy and on the differential response of tumor cells residing in different MMEs to antitumor therapy. Finally, we summarize some studies dealing with the effects of the MME on a unique site‐specific metastasis—brain metastasis.

Systematic Pan-Cancer Population-Based Analysis Reveals the Incidence and Prognosis of Lung Metastases at Diagnosis

“…When the tumor grows malignantly in situ, it begins to infiltrate the surrounding tissues and enters the circulation through the blood vessel walls to form CTCs [2]. ese CTCs reach the target before the metastasis of the organ, the metastasis organ will first form the premetastasis microenvironment, and the primary tumor secretes a large number of factors, including exosomes [23,24], cytokines [2], and chemokines [9], which recruit bone-marrow-derived cells to metastatic organs and change the extracellular matrix environment of the metastatic organs. e arrival of CTC transplantation provides a living soil.…”

“…In 2020, it was reported that there were 1,806,590 new cancer cases and 606,520 cancer deaths in the USA [1]. Metastatic disease represents the most prevalent cause of cancer-related death [2]. Among the vital organs to which solid tumors metastasize, the lungs are among the most commonly affected, ranging from 20% to 45% [3].…”

Mini-Review: Can the Metastatic Cascade Be Inhibited by Targeting CD147/EMMPRIN to Prevent Tumor Recurrence?

“…The MME consists of many factors arriving from systemic factors, extracellular vesicles (EVs) secreted from the primary tumor, soluble factors secreted from the resident tissue or immune cells, and from the DTCs themselves. These prepare the pre-metastatic niche (‘soil’) to receive the metastatic cells (‘seeds’) ( 54 ), determine organotropic metastasis (affinity of DTCs to specific organs) ( 55 – 57 ), and promote tumor cell-stroma interactions ( 56 , 57 ) that eventually promote the escape of the DTCs from dormancy. However, the mechanisms that allow these myriad factors and pathways to interact and to determine dormancy or escape from it are only now beginning to be addressed.…”

Brain Vascular Microenvironments in Cancer Metastasis

“…Evidently, the pre-metastatic microenvironment is intrinsically tethered to the vasculature, both as a transport network for soluble tumour-derived factors, EVs and cells, as well as being the primary site of pre-metastatic niche formation and tumourinduced changes such as vascular leakiness and remodelling [82,83]. Site-specific tumour cell spread to the brain from primary tumours such as lung cancers, breast cancers and melanoma has been well documented in both humans and experimental models for some time [5,[84][85][86]. However, historically, little investigation has been carried out to uncover the intricacies of the brain pre-metastatic niche and how this may drive the organotropic spread observed, and it is only recently that the topic has garnered more attention.…”