Abstract
Ionising radiation (IR) is commonly used for cancer therapy; however, its potential influence on the metastatic ability of surviving cancer cells exposed directly or indirectly to IR remains controversial. Metastasis is a multistep process by which the cancer cells dissociate from the initial site, invade, travel through the blood stream or lymphatic system, and colonise distant sites. This complex process has been reported to require cancer cells to undergo epithelial-mesenchymal transition (EMT) by which the cancer cells convert from an adhesive, epithelial to motile, mesenchymal form and is also associated with changes in glycosylation of cell surface proteins, which may be functionally involved in metastasis. In this paper, we give an overview of metastatic mechanisms and of the fundamentals of cancer-associated glycosylation changes. While not attempting a comprehensive review of this wide and fast moving field, we highlight some of the accumulating evidence from in vitro and in vivo models for increased metastatic potential in cancer cells that survive IR, focusing on angiogenesis, cancer cell motility, invasion, and EMT and glycosylation. We also explore the indirect effects in cells exposed to exosomes released from irradiated cells. The results of such studies need to be interpreted with caution and there remains limited evidence that radiotherapy enhances the metastatic capacity of cancers in a clinical setting and undoubtedly has a very positive clinical benefit. However, there is potential that this therapeutic benefit may ultimately be enhanced through a better understanding of the direct and indirect effects of IR on cancer cell behaviour.
Highlights
Breast cancer is the most common cause of cancer-related death in women worldwide
Once cancer cells successfully extravasate at a distant site, it is believed that they revert to their original epithelial phenotype, termed mesenchymal-epithelial transition, MET [71]
Changes in Cancer Cell Metastatic Capacity Post-Irradiation. Since metastasis is such a complex process involving a myriad of molecular mechanisms, it is unlikely that cancer cells that have been affected by irradiation—either directly or through bystander or abscopal effects—and survived would not exhibit some alterations in their metastatic ability
Summary
Breast cancer is the most common cause of cancer-related death in women worldwide. The major risk factors are related to reproductive biology, for example, early age at menarche and late menopause, older age at first full term pregnancy or nulliparity, and use of hormone-based medication. It has well been established that ionising irradiation can be implicated in breast cancer induction. Women exposed to IR when older than 50 years show no significant increase in breast cancer risk following irradiation [2]. Mammary carcinogenic risk and susceptibility often increase during the cell proliferation period [4,5], during which DNA synthesis and replication increase. This can lead to Cancers 2020, 12, 236; doi:10.3390/cancers12010236 www.mdpi.com/journal/cancers. Cancers 2020, 12, 236 a higher chance of DNA damage to the offspring cells [6]. RT outcome is clinically based on radiation type, doses, fractions, tumour replication time, hypoxia, and radiosensitivity of the tumour [18]
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