Cancer-associated fibroblast-derived exosome microRNA-21 promotes angiogenesis in multiple myeloma

Abstract

Multiple myeloma (MM) is the second most common hematological malignancy, and angiogenesis determines its progression. In the tumor microenvironment, normal fibroblasts (NFs) are transformed into cancer-associated fibroblasts (CAFs), which can promote angiogenesis. Microribonucleic acid-21 (miR-21) is highly expressed in various tumors. However, research on the relationship between tumor angiogenesis and miR-21 is rare. We analyzed the relationship between miR-21, CAFs, and angiogenesis in MM. NFs and CAFs were isolated from the bone marrow fluids of patients with dystrophic anemia and newly-diagnosed MM. Co-culturing of CAF exosomes with multiple myeloma endothelial cells (MMECs) showed that CAF exosomes were able to enter MMECs in a time-dependent manner and initiate angiogenesis by promoting proliferation, migration, and tubulogenesis. We found that miR-21 was abundant in CAF exosomes, entering MMECs and regulating angiogenesis in MM. By transfecting NFs with mimic NC, miR-21 mimic, inhibitor NC, and miR-21 inhibitor, we found that miR-21 significantly increased the expression of alpha-smooth muscle actin and fibroblast activation protein in NFs. Our results showed that miR-21 can transform NFs into CAFs, and that CAF exosomes promote angiogenesis by carrying miR-21 into MMECs. Therefore, CAF-derived exosomal miR-21 may serve as a novel diagnostic biomarker and therapeutic target for MM.

Exosomes: a promising avenue for cancer diagnosis beyond treatment

“…Of note, the exosome is promising for the cancer diagnostics ( Si et al, 2023 ). Exosomes derived from cancer cells contain specific biomarkers, such as mutant DNA, proteins, and microRNAs, that can serve as indicators of cancer presence and progression ( Ji et al, 2013 ; Miaomiao et al, 2023 ). Liquid biopsies based on exosome cargo analysis offer non-invasive methods for early cancer detection and monitoring treatment responses ( Feng et al, 2019 ).…”

The hidden messengers: cancer associated fibroblasts—derived exosomal miRNAs as key regulators of cancer malignancy

“…Researchers have found that exosomal miRNAs derived from CAFs can also participate in the process of promoting tumor angiogenesis. For example, CAF-derived exosomes promote angiogenesis by delivering miR-21 to endothelial cells in multiple myeloma ( Miaomiao et al, 2023 ). miR-135b-5p is upregulated, promoting angiogenesis in CRC cells by inhibiting thioredoxin-interacting proteins ( Yin et al, 2021 ).…”

Exosome nanovesicles: biomarkers and new strategies for treatment of human diseases

“…With a full understanding of the relationship between exosomal contents and disease occurrence, exosomes are considered potential therapeutic targets and biomarkers. 161 Moreover, it stably exists in various body fluids and has the advantages of high sensitivity, low invasiveness, and easy access to materials compared with other tests, 17 which can help in the early diagnosis of diseases, detection of diseases, and evaluation of therapeutic effects (Table 1 ). 32 , 162 …”