Exosomes: Mediators in microenvironment of colorectal cancer

Abstract

Tumor microenvironment, the soil where tumor thrives, plays a critical role in the development and progression of colorectal cancer (CRC). Various cell signaling molecules in the environment promote tumor angiogenesis, immune tolerance and facilitate immune escape. Exosomes, as messengers between tumor and host cells, are considered key mediators involved in the tumor-accelerating environment. However, the exosome-mediated communication networks in the CRC microenvironment are still largely unclear. In this review, we summarized the relationship between TME and CRC based on recent literature. Then, we revealed the unique impacts and signal molecules of exosomes on account of their regulatory role in the flora, hypoxia, inflammatory and immunological microenvironment of CRC. Finally, we summarized the therapeutically effective of exosomes in CRC microenvironment and discussed their current status and prospects, aiming to provide new molecular targets and a theoretical basis for the CRC treatment.

Function and mechanism of exosomes derived from different cells as communication mediators in colorectal cancer metastasis

“…In addition to exosomal miRNAs, other genetic or metabolic molecules present in tumor-derived exosomes, such as lncRNAs, circRNAs, and others, exert regulatory effects on the metastasis of CRC through various mechanisms including immune evasion. 18 , 99 The plasma level of exosomal lncRPPH1 was elevated in untreated patients with CRC and significantly decreased following tumor resection. Exosomes derived from CRC cells facilitated the transfer of lncRPPH1 into macrophages, leading to M2 polarization and consequently promoting CRC cells metastasis and proliferation.…”

“… 15 , 16 Cellular communication encompasses diverse mechanisms, including direct cell-to-cell interactions and indirect regulation mediated by secreted bioactive molecule or extracellular vesicle (EV), thereby reshaping TME and exerting multifaceted influences on tumor development, encompassing cancer cell proliferation, invasion, metastasis, immune escape, angiogenesis, and chemotherapy resistance. 17 , 18 …”

“…These effects encompass migratory potential acquisition from the primary tumor, promotion of angiogenesis, evasion of immune surveillance, organ-specific metastasis patterns, establishment of pre-metastatic niches, and growth initiation at secondary sites. 18 , 30 Tumor-derived exosomes (TDEs) play a pivotal role in creating a conducive microenvironment at future metastatic sites while also mediating non-random patterns of metastasis by selectively targeting organs such as lung or liver based on their integrin composition. 28 Other cells within the TME, including cancer-associated fibroblasts (CAFs) and macrophages, also play crucial roles in different stages of cancer progression and metastasis.…”

“… 30 Exosomes enable the transmission of biological signals between different types of cells or tissues, and their regulation of intracellular signaling pathways enhances their potential diagnostic value and therapeutic efficacy in various diseases, including cancer. 18 , 23 Exosomes can be detected in a diverse range of human bodily fluids, and their isolation through liquid biopsies provides a convenient approach to acquire comprehensive genetic and metabolic information using various detection methodologies. 23 The primary potential of exosome-based liquid biopsy lies in its capability for disease status determination and stage diagnosis.…”

Resting natural killer cells promote the progress of colon cancer liver metastasis by elevating tumor-derived sSCF

“…The tumor microenvironment (TME) is a dynamic environment that governs tumor behavior and is required for tumor cell survival, growth, proliferation, and metastasis (Yao et al, 2023) . Unlike previous understanding, it has recently been proposed that certain immune cells present in the TME (such as myeloid-derived suppressor cells (Liu et al, 2023) , macrophages (Ngambenjawong et al, 2017) , neutrophils (Li et al, 2019) , and CD8 + T cells (Tiberti et al, 2022) ) favor tumor progression.…”