TSG6 affects anti cancer drug resistance and angiogenesis in 3D spheroid model of canine mammary gland tumor cells
Abstract TSG6 (Tumor necrosis factor stimulated gene-6) plays a critical role in modulating the tumor microenvironment by regulating inflammation, immune responses, and extracellular matrix remodeling. Hypoxia affects tumor growth, angiogenesis, and anti-cancer drug resistance in the tumor microenvi...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-08-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-12950-3 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849226349296746496 |
|---|---|
| author | Ga-Hyun Lim Ju-Hyun An Jeong-Hwa Lee Kyoung-Won Seo Hwa-Young Youn |
| author_facet | Ga-Hyun Lim Ju-Hyun An Jeong-Hwa Lee Kyoung-Won Seo Hwa-Young Youn |
| author_sort | Ga-Hyun Lim |
| collection | DOAJ |
| description | Abstract TSG6 (Tumor necrosis factor stimulated gene-6) plays a critical role in modulating the tumor microenvironment by regulating inflammation, immune responses, and extracellular matrix remodeling. Hypoxia affects tumor growth, angiogenesis, and anti-cancer drug resistance in the tumor microenvironment, and TSG6 expression is known to influence HIF-1α expression in tumor tissues. In this study, we created TSG6 knockdown spheroids of canine mammary gland tumor (MGT) cells (CIPp and CIPm) to investigate the effects of TSG6 on angiogenesis and drug resistance in the tumor microenvironment. Using a siRNA transfection system, we induced TSG6 knockdown in canine MGT cells and formed TSG6 knockdown spheroids using an ultra-low adhesion plate. Cell viability and apoptosis were assessed by treating TSG6 knockdown spheroids with doxorubicin. Angiogenesis was evaluated by forming vascularized spheroids with canine MGT and endothelial cells (ECs). TSG6 knockdown led to reduced expression of tumor growth factors and multidrug resistance genes in canine MGT cells, as well as a significant reduction in hypoxic conditions within the spheroids. When treated with doxorubicin, TSG6 knockdown spheroids exhibited decreased viability and increased apoptosis. In a vascularized TSG6 knockdown spheroid model, TSG6 knockdown significantly reduced the expression of CD31 and tube formation in canine ECs. In conclusion, we created a TSG6 knockdown spheroid model to investigate the role of TSG6 in the tumor microenvironment. TSG6 knockdown significantly reduced anti-cancer drug resistance and angiogenesis in canine MGT cells. Therefore, TSG6 could be considered a potential therapeutic target for canine MGT. |
| format | Article |
| id | doaj-art-52ae2ae743654bd1ad49fa1fcbb3d8a9 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-52ae2ae743654bd1ad49fa1fcbb3d8a92025-08-24T11:22:07ZengNature PortfolioScientific Reports2045-23222025-08-0115111310.1038/s41598-025-12950-3TSG6 affects anti cancer drug resistance and angiogenesis in 3D spheroid model of canine mammary gland tumor cellsGa-Hyun Lim0Ju-Hyun An1Jeong-Hwa Lee2Kyoung-Won Seo3Hwa-Young Youn4Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Science, College of Veterinary Medicine, Seoul National UniversityDepartment of Veterinary Emergency and Critical Care Medicine, Institute of Veterinary Science, College of Veterinary Medicine, Kangwon National UniversityK-BIO KIURI Center, Seoul National UniversityLaboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Science, College of Veterinary Medicine, Seoul National UniversityLaboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Science, College of Veterinary Medicine, Seoul National UniversityAbstract TSG6 (Tumor necrosis factor stimulated gene-6) plays a critical role in modulating the tumor microenvironment by regulating inflammation, immune responses, and extracellular matrix remodeling. Hypoxia affects tumor growth, angiogenesis, and anti-cancer drug resistance in the tumor microenvironment, and TSG6 expression is known to influence HIF-1α expression in tumor tissues. In this study, we created TSG6 knockdown spheroids of canine mammary gland tumor (MGT) cells (CIPp and CIPm) to investigate the effects of TSG6 on angiogenesis and drug resistance in the tumor microenvironment. Using a siRNA transfection system, we induced TSG6 knockdown in canine MGT cells and formed TSG6 knockdown spheroids using an ultra-low adhesion plate. Cell viability and apoptosis were assessed by treating TSG6 knockdown spheroids with doxorubicin. Angiogenesis was evaluated by forming vascularized spheroids with canine MGT and endothelial cells (ECs). TSG6 knockdown led to reduced expression of tumor growth factors and multidrug resistance genes in canine MGT cells, as well as a significant reduction in hypoxic conditions within the spheroids. When treated with doxorubicin, TSG6 knockdown spheroids exhibited decreased viability and increased apoptosis. In a vascularized TSG6 knockdown spheroid model, TSG6 knockdown significantly reduced the expression of CD31 and tube formation in canine ECs. In conclusion, we created a TSG6 knockdown spheroid model to investigate the role of TSG6 in the tumor microenvironment. TSG6 knockdown significantly reduced anti-cancer drug resistance and angiogenesis in canine MGT cells. Therefore, TSG6 could be considered a potential therapeutic target for canine MGT.https://doi.org/10.1038/s41598-025-12950-3AngiogenesisAnti-cancer drug resistanceCanine mammary gland tumorTSG6Tumor microenvironmentSpheroid |
| spellingShingle | Ga-Hyun Lim Ju-Hyun An Jeong-Hwa Lee Kyoung-Won Seo Hwa-Young Youn TSG6 affects anti cancer drug resistance and angiogenesis in 3D spheroid model of canine mammary gland tumor cells Scientific Reports Angiogenesis Anti-cancer drug resistance Canine mammary gland tumor TSG6 Tumor microenvironment Spheroid |
| title | TSG6 affects anti cancer drug resistance and angiogenesis in 3D spheroid model of canine mammary gland tumor cells |
| title_full | TSG6 affects anti cancer drug resistance and angiogenesis in 3D spheroid model of canine mammary gland tumor cells |
| title_fullStr | TSG6 affects anti cancer drug resistance and angiogenesis in 3D spheroid model of canine mammary gland tumor cells |
| title_full_unstemmed | TSG6 affects anti cancer drug resistance and angiogenesis in 3D spheroid model of canine mammary gland tumor cells |
| title_short | TSG6 affects anti cancer drug resistance and angiogenesis in 3D spheroid model of canine mammary gland tumor cells |
| title_sort | tsg6 affects anti cancer drug resistance and angiogenesis in 3d spheroid model of canine mammary gland tumor cells |
| topic | Angiogenesis Anti-cancer drug resistance Canine mammary gland tumor TSG6 Tumor microenvironment Spheroid |
| url | https://doi.org/10.1038/s41598-025-12950-3 |
| work_keys_str_mv | AT gahyunlim tsg6affectsanticancerdrugresistanceandangiogenesisin3dspheroidmodelofcaninemammaryglandtumorcells AT juhyunan tsg6affectsanticancerdrugresistanceandangiogenesisin3dspheroidmodelofcaninemammaryglandtumorcells AT jeonghwalee tsg6affectsanticancerdrugresistanceandangiogenesisin3dspheroidmodelofcaninemammaryglandtumorcells AT kyoungwonseo tsg6affectsanticancerdrugresistanceandangiogenesisin3dspheroidmodelofcaninemammaryglandtumorcells AT hwayoungyoun tsg6affectsanticancerdrugresistanceandangiogenesisin3dspheroidmodelofcaninemammaryglandtumorcells |