Matrix metalloproteinase 13‐containing exosomes promote nasopharyngeal carcinoma metastasis

Abstract

Nasopharyngeal cancer (NPC) is an endemic type of head and neck cancer with a high rate of cervical lymph node metastasis. Metastasis is the major cause of death in NPC patients. Increasing evidence indicates that exosomes play a pivotal role in promoting cancer metastasis by enhancing angiogenesis and ECM degradation. Matrix metalloproteinase 13 is an important kind of matrix proteinase that is often overexpressed in various tumors and increases the risk of metastasis. However, little is known about the potential role of MMP13‐containing exosomes in NPC. In this study, we found that MMP13 was overexpressed in NPC cells and exosomes purified from conditioned medium (CM) as well as NPC patients’ plasma. Transwell analysis revealed that MMP13‐containing exosomes facilitated the metastasis of NPC cells. Furthermore, siRNA inhibited the effect of MMP13‐containing exosomes on tumor cells metastasis as well as angiogenesis. The current findings provided novel insight into the vital role of MMP13‐containing exosomes in NPC progression which might offer unique insights for potential therapeutic strategies for NPC progressions.

Conceptual Analogies Between Multi-Scale Feeding and Feedback Cycles in Supermassive Black Hole and Cancer Environments

“…Furthermore, exosomes-based intratumor communication is also fundamental for the acquisition of migratory properties in cancer cells from the primary tumor. This phenomenon has been reported in both nasopharyngeal carcinoma (12) and prostate cancer (13), where exosomes released by primary tumor cells can increase the invasiveness and motility of other recipient malignant cells (Figure 2).…”

“…As reported above, tumor-derived exosomes promotes the invasiveness and motility of tumor cells from the primary site to metastatic niches ( 12 , 13 ) ( Figure 2 ). By analyzing different cell lines, Yu et al ( 31 ) observed 79 proteins that were differently expressed in exosomes between more and less metastatic tumors, and these proteins were implicated in cell adhesion, invasion, growth, metabolism and metastasis ( 31 ).…”

Conceptual Analogies Between Multi-Scale Feeding and Feedback Cycles in Supermassive Black Hole and Cancer Environments

“…Furthermore, exosomes-based intratumor communication is also fundamental for the acquisition of migratory properties in cancer cells from the primary tumor. This phenomenon has been reported in both nasopharyngeal carcinoma (12) and prostate cancer (13), where exosomes released by primary tumor cells can increase the invasiveness and motility of other recipient malignant cells (Figure 2).…”

“…As reported above, tumor-derived exosomes promotes the invasiveness and motility of tumor cells from the primary site to metastatic niches ( 12 , 13 ) ( Figure 2 ). By analyzing different cell lines, Yu et al ( 31 ) observed 79 proteins that were differently expressed in exosomes between more and less metastatic tumors, and these proteins were implicated in cell adhesion, invasion, growth, metabolism and metastasis ( 31 ).…”

Tumor-Derived Exosomes Mediate the Instability of Cadherins and Promote Tumor Progression

“…High expression of MMP13 in exosomes secreted by NPCs cells was considered to play an important role in these processes. Exosomes released from MMP-13 silenced NPC cells reversed EMT compared with normal NPC cells, confirming the positive relationship between MMP-13 and EMT [110]. On the basis of this work, Shan et al found that hypoxic conditions promoted the expression of MMP-13 in NPC cells, and more MMP13 was encapsulated in exosomes and delivered to recipient cells [111].…”

Small Extracellular Vesicles and Metastasis—Blame the Messenger

“…Interestingly, a study by Yokoi and colleagues in 2017 established that sEVs may play a crucial role in fostering MMP activity. Here, no MMP protein was found in sEVs, as shown in various studies [97][98][99], but the selective packaging of MMP1 mRNA into sEVs derived from ovarian cancer (OC) cells was found. These sEVs then triggered destruction of the peritoneal mesothelium and BM in vitro and in vivo, ultimately promoting metastatic behavior [100].…”

Conceptual Analogies Between Multi-Scale Feeding and Feedback Cycles in Supermassive Black Hole and Cancer Environments

“…Furthermore, exosomes-based intratumor communication is also fundamental for the acquisition of migratory properties in cancer cells from the primary tumor. This phenomenon has been reported in both nasopharyngeal carcinoma (12) and prostate cancer (13), where exosomes released by primary tumor cells can increase the invasiveness and motility of other recipient malignant cells (Figure 2).…”

“…As reported above, tumor-derived exosomes promotes the invasiveness and motility of tumor cells from the primary site to metastatic niches ( 12 , 13 ) ( Figure 2 ). By analyzing different cell lines, Yu et al ( 31 ) observed 79 proteins that were differently expressed in exosomes between more and less metastatic tumors, and these proteins were implicated in cell adhesion, invasion, growth, metabolism and metastasis ( 31 ).…”

Tumor-Derived Exosomes Mediate the Instability of Cadherins and Promote Tumor Progression

“…High expression of MMP13 in exosomes secreted by NPCs cells was considered to play an important role in these processes. Exosomes released from MMP-13 silenced NPC cells reversed EMT compared with normal NPC cells, confirming the positive relationship between MMP-13 and EMT [110]. On the basis of this work, Shan et al found that hypoxic conditions promoted the expression of MMP-13 in NPC cells, and more MMP13 was encapsulated in exosomes and delivered to recipient cells [111].…”

Small Extracellular Vesicles and Metastasis—Blame the Messenger

“…Interestingly, a study by Yokoi and colleagues in 2017 established that sEVs may play a crucial role in fostering MMP activity. Here, no MMP protein was found in sEVs, as shown in various studies [97][98][99], but the selective packaging of MMP1 mRNA into sEVs derived from ovarian cancer (OC) cells was found. These sEVs then triggered destruction of the peritoneal mesothelium and BM in vitro and in vivo, ultimately promoting metastatic behavior [100].…”

Conceptual Analogies Between Multi-Scale Feeding and Feedback Cycles in Supermassive Black Hole and Cancer Environments

“…Furthermore, exosomes-based intratumor communication is also fundamental for the acquisition of migratory properties in cancer cells from the primary tumor. This phenomenon has been reported in both nasopharyngeal carcinoma (12) and prostate cancer (13), where exosomes released by primary tumor cells can increase the invasiveness and motility of other recipient malignant cells (Figure 2).…”

“…As reported above, tumor-derived exosomes promotes the invasiveness and motility of tumor cells from the primary site to metastatic niches ( 12 , 13 ) ( Figure 2 ). By analyzing different cell lines, Yu et al ( 31 ) observed 79 proteins that were differently expressed in exosomes between more and less metastatic tumors, and these proteins were implicated in cell adhesion, invasion, growth, metabolism and metastasis ( 31 ).…”

Tumor-Derived Exosomes Mediate the Instability of Cadherins and Promote Tumor Progression

“…High expression of MMP13 in exosomes secreted by NPCs cells was considered to play an important role in these processes. Exosomes released from MMP-13 silenced NPC cells reversed EMT compared with normal NPC cells, confirming the positive relationship between MMP-13 and EMT [110]. On the basis of this work, Shan et al found that hypoxic conditions promoted the expression of MMP-13 in NPC cells, and more MMP13 was encapsulated in exosomes and delivered to recipient cells [111].…”

Small Extracellular Vesicles and Metastasis—Blame the Messenger

“…Interestingly, a study by Yokoi and colleagues in 2017 established that sEVs may play a crucial role in fostering MMP activity. Here, no MMP protein was found in sEVs, as shown in various studies [97][98][99], but the selective packaging of MMP1 mRNA into sEVs derived from ovarian cancer (OC) cells was found. These sEVs then triggered destruction of the peritoneal mesothelium and BM in vitro and in vivo, ultimately promoting metastatic behavior [100].…”