Exosomes, miRNAs and Cancer

In a recent Science article there is a discussion of exosomes and miRNAs in the context of cancer metastasis.

The discussion presents the exosome as a vehicle to transport miRNAs across intercellular borders and create effects at distant cells which are malignant in nature. We have seen this concept in another venue, that of the stem cell. Thus is we have a cancer that has a stem cell basis, then perhaps they way it functions is as an exosome creator transmitting miRNAs, such as miR-34, to other cells, creating malignant cell growth.

The article states:

Melo et al. reveal a role of exosomes in cell-independent miRNA biogenesis that affects cancer progression. The authors show that only exosomes derived from cancer cells, but not those derived from normal cells, contain key enzymes involved in miRNA biogenesis such as Dicer, TAR (trans-activation response) RNA-binding protein (TRBP), and AGO2 (see the first figure). The exosomes also contain the membrane protein CD43, which plays a role in accumulating Dicer in cancer exosomes. The study also shows that Dicer-containing cancer exosomes process precursor miRNAs into mature miRNAs (including oncomiRs) over time, and upon encounter with normal human mammary epithelial, cells induces them to become cancerous. Healthy mammary human epithelial cells formed tumors when they were injected into mice that were treated with cancer exosomes. Moreover, miRNAs in the cancer exosomes inhibited the expression of their respective mRNA targets—phosphatase and tensin homolog [(PTEN), a tumor suppressor protein] and the transcription factor homeobox D10 (HOXD10)—in the recipient epithelial cells. The authors suggest a possible temporal oncogenic “field effect” induced by cancer exosomes that recruits surrounding normal cells to become tumorigenic. The tantalizing results of Fabbri et al. and Melo et al. merit further investigation in immunocompetent mouse models. 

This should be an interesting alternative to many other models.

Also it should be seen that this model must be incorporated into what some have done to develop systems models for cancer. The exosome then becomes an additional metastatic transport mechanism that has characteristics differing from those of cells, and especially for transport in the blood.