Suppression of colorectal cancer liver metastasis by apolipoprotein(a) kringle V in a nude mouse model through the induction of apoptosis in tumor-associated endothelial cells.
The formation of liver metastases in colorectal cancer patients is the primary cause of patient death. Current therapies directed at liver metastasis from colorectal cancer have had minimal impact on patient outcomes. Therefore, the development of alternative treatment strategies for liver metastasi...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3974802?pdf=render |
| _version_ | 1818995684053876736 |
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| author | Jin-Hyung Ahn Hyun-Kyung Yu Ho-Jeong Lee Soon Won Hong Sun Jin Kim Jang-Seong Kim |
| author_facet | Jin-Hyung Ahn Hyun-Kyung Yu Ho-Jeong Lee Soon Won Hong Sun Jin Kim Jang-Seong Kim |
| author_sort | Jin-Hyung Ahn |
| collection | DOAJ |
| description | The formation of liver metastases in colorectal cancer patients is the primary cause of patient death. Current therapies directed at liver metastasis from colorectal cancer have had minimal impact on patient outcomes. Therefore, the development of alternative treatment strategies for liver metastasis is needed. In the present study, we demonstrated that recombinant human apolipoprotein(a) kringle V, also known as rhLK8, induced the apoptotic turnover of endothelial cells in vitro through the mitochondrial apoptosis pathway. The interaction of rhLK8 with glucose-regulated protein 78 (GRP78) may be involved in the induction of apoptosis because the inhibition of GRP78 by GRP78-specific antibodies or siRNA knockdown inhibited the rhLK8-mediated apoptosis of human umbilical vein endothelial cells in vitro. Next, to evaluate the effects of rhLK8 on angiogenesis and metastasis, an experimental model of liver metastasis was established by injecting a human colorectal cancer cell line, LS174T, into the spleens of BALB/c nude mice. The systemic administration of rhLK8 significantly suppressed liver metastasis from human colorectal cancer cells and improved host survival compared with controls. The combination of rhLK8 and 5-fluorouracil substantially increased these survival benefits compared with either therapy alone. Histological observation showed significant induction of apoptosis among tumor-associated endothelial cells in liver metastases from rhLK8-treated mice compared with control mice. Collectively, these results suggest that the combination of rhLK8 with conventional chemotherapy may be a promising approach for the treatment of patients with life-threatening colorectal cancer liver metastases. |
| first_indexed | 2024-12-20T21:17:45Z |
| format | Article |
| id | doaj.art-d037d8ef20d44670a937cb473911a300 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T21:17:45Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-d037d8ef20d44670a937cb473911a3002022-12-21T19:26:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9379410.1371/journal.pone.0093794Suppression of colorectal cancer liver metastasis by apolipoprotein(a) kringle V in a nude mouse model through the induction of apoptosis in tumor-associated endothelial cells.Jin-Hyung AhnHyun-Kyung YuHo-Jeong LeeSoon Won HongSun Jin KimJang-Seong KimThe formation of liver metastases in colorectal cancer patients is the primary cause of patient death. Current therapies directed at liver metastasis from colorectal cancer have had minimal impact on patient outcomes. Therefore, the development of alternative treatment strategies for liver metastasis is needed. In the present study, we demonstrated that recombinant human apolipoprotein(a) kringle V, also known as rhLK8, induced the apoptotic turnover of endothelial cells in vitro through the mitochondrial apoptosis pathway. The interaction of rhLK8 with glucose-regulated protein 78 (GRP78) may be involved in the induction of apoptosis because the inhibition of GRP78 by GRP78-specific antibodies or siRNA knockdown inhibited the rhLK8-mediated apoptosis of human umbilical vein endothelial cells in vitro. Next, to evaluate the effects of rhLK8 on angiogenesis and metastasis, an experimental model of liver metastasis was established by injecting a human colorectal cancer cell line, LS174T, into the spleens of BALB/c nude mice. The systemic administration of rhLK8 significantly suppressed liver metastasis from human colorectal cancer cells and improved host survival compared with controls. The combination of rhLK8 and 5-fluorouracil substantially increased these survival benefits compared with either therapy alone. Histological observation showed significant induction of apoptosis among tumor-associated endothelial cells in liver metastases from rhLK8-treated mice compared with control mice. Collectively, these results suggest that the combination of rhLK8 with conventional chemotherapy may be a promising approach for the treatment of patients with life-threatening colorectal cancer liver metastases.http://europepmc.org/articles/PMC3974802?pdf=render |
| spellingShingle | Jin-Hyung Ahn Hyun-Kyung Yu Ho-Jeong Lee Soon Won Hong Sun Jin Kim Jang-Seong Kim Suppression of colorectal cancer liver metastasis by apolipoprotein(a) kringle V in a nude mouse model through the induction of apoptosis in tumor-associated endothelial cells. PLoS ONE |
| title | Suppression of colorectal cancer liver metastasis by apolipoprotein(a) kringle V in a nude mouse model through the induction of apoptosis in tumor-associated endothelial cells. |
| title_full | Suppression of colorectal cancer liver metastasis by apolipoprotein(a) kringle V in a nude mouse model through the induction of apoptosis in tumor-associated endothelial cells. |
| title_fullStr | Suppression of colorectal cancer liver metastasis by apolipoprotein(a) kringle V in a nude mouse model through the induction of apoptosis in tumor-associated endothelial cells. |
| title_full_unstemmed | Suppression of colorectal cancer liver metastasis by apolipoprotein(a) kringle V in a nude mouse model through the induction of apoptosis in tumor-associated endothelial cells. |
| title_short | Suppression of colorectal cancer liver metastasis by apolipoprotein(a) kringle V in a nude mouse model through the induction of apoptosis in tumor-associated endothelial cells. |
| title_sort | suppression of colorectal cancer liver metastasis by apolipoprotein a kringle v in a nude mouse model through the induction of apoptosis in tumor associated endothelial cells |
| url | http://europepmc.org/articles/PMC3974802?pdf=render |
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