Presumed Roles of APRO Family Proteins in Cancer Invasiveness

Abstract

The APRO family members may be involved in the regulation of cell growth, migration, and/or invasion. Although an APRO protein could suppress the invasiveness of several cancer cells, it has been reported that overexpression of the same APRO protein could also promote the invasiveness and/or metastasis of the same cancer cells. In general, the invasiveness of cancer cells might be associated with the function of matrix metalloproteinases (MMPs) as well as with the function of certain exosomes. However, it has been shown that exosomes involving particular APRO proteins, MMPs, and/or microRNA could contribute to the regulation of invasiveness. Here, we discuss contradictory reports on invasiveness in relation to APRO family proteins on the basis of understanding the function of MMPs and/or various exosomes. A better understanding of those mechanisms could be of use to bring about innovative strategies for cancer treatment.

Keywords: APRO protein; exosome; matrix metalloproteinase; microRNA; tissue inhibitors of metalloproteinase.

Figure 1

Hypothetical schematic image of the relationship among the APRO proteins (APROs), exosomes, immune cells, immune check point PD-L1 on stromal fibroblasts, and the cancer cells’ invasion/metastasis. Indicated molecules are examples. Arrowhead means stimulation, whereas hammerhead represents inhibition. Note that some critical pathways such as inflammation activation and/or cancer cell growth pathway have been omitted for clarity. Abbreviations: APROs—APRO family proteins; miRNAs—microRNAs; MMPs—matrix metalloproteinases; PD-L1—programmed cell-death ligand 1.

Figure 2

Although APRO family proteins (APROs) could individually inhibit the progression, invasion, and/or metastasis of cancer cells, the other conditions such as the expression levels of MMPs or TIMPs, the presence of some exosomes, and/or the function of microRNAs (miRNAs) or specific proteins in the exosomes could further alter the effect of APRO proteins, either of promotion or inhibition, on the invasiveness of cancer cells. Indicated molecules are examples. Arrowhead means stimulation, whereas hammerhead represents inhibition. Note that some critical pathways have been omitted for clarity. Abbreviations: APROs—APRO family proteins; miRNAs—microRNAs; MMPs—matrix metalloproteinases; TIMPs—tissue inhibitors of metalloproteinases.