Department of Cancer Molecular Biology, Institution of Health Sciences, Pamukkale University, Denizli, Turkey.
Department of Medical Genetics, Faculty of MedicinePamukkale University, Denizli, Turkey.
Chem Biol Drug Des. 2023 Jul;102(1):65-75. doi: 10.1111/cbdd.14245. Epub 2023 Apr 29.
MYC amplification and overexpression in breast cancer occur 16% and 22%, respectively, and MYC has a linchpin role in breast carcinogenesis. Emerging evidence has started to shed light on central role of MYC in breast cancer progression. On the contrary, tumor-derived exosomes and their cargo molecules are required for the modulation of the tumor environment and to promote carcinogenesis. Still, how MYC regulates tumor-derived exosomes is still a matter of investigation in the context of breast cancer. Here, we investigated for the first time how MYC affects the biological functions of normal breast cells cocultured with exosomes derived from MYC-expression manipulated breast cancer cells. Accordingly, exosomes were isolated from MCF-7 and MDA-MB-231 cells that MYC expression was manipulated through siRNAs or lentiviral vectors by using exosome isolation reagent. Then, normal breast epithelial MCF-10A cells were treated with breast cancer cell-derived exosomes. The cellular activity of MCF-10A was investigated by cell growth assay, wound healing assay, and transwell assay. Our results suggested that MCF-10A cells treated with exosomes derived from MYC-overexpressing breast cancer cells demonstrated higher proliferation and migration capability compared with nontreated cells. Likewise, MCF-10A cells treated with exosomes derived from MYC-silenced cancer cells did not show high proliferation and invasive capacity. Overall, MYC can drive the functions of exosomes secreted from breast cancer cells. This may allow exploring a new mechanism how tumor cells regulate cancer progression and modulate tumor environment. The present study clears the way for further researches as in vivo studies and multi-omics that clarify exosomal content in an MYC-dependent manner.
在乳腺癌中，MYC 扩增和过表达分别发生在 16%和 22%，并且 MYC 在乳腺癌发生中起着关键作用。新出现的证据开始揭示 MYC 在乳腺癌进展中的核心作用。相反，肿瘤衍生的外泌体及其 cargo 分子对于调节肿瘤微环境和促进癌变是必需的。尽管如此，MYC 如何调节肿瘤衍生的外泌体仍然是乳腺癌背景下的一个研究课题。在这里，我们首次研究了 MYC 如何影响与 MYC 表达操纵的乳腺癌细胞来源的外泌体共培养的正常乳腺细胞的生物学功能。因此，通过使用外泌体分离试剂，从 MYC 表达通过 siRNA 或慢病毒载体操纵的 MCF-7 和 MDA-MB-231 细胞中分离出外泌体。然后，用乳腺癌细胞来源的外泌体处理正常乳腺上皮 MCF-10A 细胞。通过细胞生长测定、划痕愈合测定和 Transwell 测定来研究 MCF-10A 细胞的细胞活性。我们的结果表明，与未处理的细胞相比，用来自过表达 MYC 的乳腺癌细胞来源的外泌体处理的 MCF-10A 细胞表现出更高的增殖和迁移能力。同样，用沉默了 MYC 的癌细胞来源的外泌体处理的 MCF-10A 细胞没有表现出高增殖和侵袭能力。总的来说，MYC 可以驱动乳腺癌细胞分泌的外泌体的功能。这可能允许探索一种新的机制，即肿瘤细胞如何调节癌症进展和调节肿瘤微环境。本研究为进一步的研究铺平了道路，如体内研究和多组学研究，以明确依赖于 MYC 的外泌体内容。
