Metastatic organotropism: a brief overview

Abstract

Organotropism has been known since 1889, yet this vital component of metastasis has predominantly stayed elusive. This mini-review gives an overview of the current understanding of the underlying mechanisms of organotropism and metastases development by focusing on the formation of the pre-metastatic niche, immune defenses against metastases, and genomic alterations associated with organotropism. The particular case of brain metastases is also addressed, as well as the impact of organotropism in cancer therapy. The limited comprehension of the factors behind organotropism underscores the necessity for efficient strategies and treatments to manage metastases.

Keywords: brain metastasis; immune response to metastasis; metastasis; organotropism; pre-metastatic niche.

Figure 1

Relationship between the causes (Why it happens) and the cellular and molecular mechanisms of metastasis organotropism (How it happens). Anatomic relations between primary tumor and metastasis locations partially explain organotropism patterns through a facilitated accessibility of circulating tumor cells (CTCs) to particular metastatic locations. Properties of the primary tumor cell type, even before changes induced by tumorigenesis, can already explain a better metabolic adaptation or intercellular communication at the preferred metastatic niches. Finally, genomic alterations, such as mutations and copy number variations, can occur in the initial primary tumor development, subsequently in specific subclones of the primary tumor or are only acquired during tumor cell dissemination or metastasis colonization. These genomic alterations can modify cancer cell properties and favor specific metastatic locations through the secretion of tumor-derived signals or extracellular vesicles that can recruit and reprogram immune and stromal cells at the metastatic site, even before the arrival of CTCs. These reprogrammed cells can be, for example, bone marrow derived cells, cancer associated fibroblasts, dendritic cells, neutrophils or macrophages. They become pro-metastatic and induce processes like extracellular matrix (ECM) remodeling, immunosuppression, inflammation and angiogenesis. These processes facilitate the arrival and survival of CTCs at the metastatic niche.