1.Metastasis prognostic factors and cancer stem cell-related transcription factors associated with metastasis induction in canine metastatic mammary gland tumors
Saetbyul KIM ; Eunyeong BOK ; Sangyeob LEE ; Hyeon-Jeong LEE ; Yongho CHOE ; Na-Hyun KIM ; Won-Jae LEE ; Gyu-Jin RHO ; Sung-Lim LEE
Journal of Veterinary Science 2021;22(5):e62-
Background:
Canine mammary gland tumor (MGT) is the most common cancer in aged female dogs. Although it's important to identify reliable metastasis or prognostic factors by evaluating related to cell division, adhesion, and cancer stem cell-related transcription factor (TF) in metastasis-induced canine MGT, but there are limited studies.
Objectives:
We aimed to identify metastasis prognostic factors and cancer stem cell-TFs in canine MGTs.
Methods:
Age-matched female dogs diagnosed with MGT only were classified into metastatic and non-metastatic groups by histopathological staining of MGT tissues. The mRNA levels of cancer prognostic metastasis molecular factors (E-cadherin, ICAM-1, PRR14, VEGF, HPRT1, RPL4 and hnRNP H ) and cancer stem cell-related TFs (Oct4, Sox2, and Nanog ) were compared between metastatic and non-metastatic canine MGT tissues using qRT-PCR analysis.
Results:
The mRNA levels of ICAM-1, PRR14, VEGF, hnRNP H, Oct4, Sox2, and Nanog in metastatic MGT group were significantly higher than those in non-metastatic MGT group. However, mRNA level of RPL4 was significantly lower in metastatic MGT group. Loss of E-cadherin and HPRT1 was observed in the metastatic MGT group but it was not significant.
Conclusions
Consistent expression patterns of all metastasis-related factors showing elevation in ICAM-1, PRR14, VEGF, hnRNP H, Oct4, Sox2, and Nanog, but decreases in RPL4 levels occurred in canine MGT tissues, which was associated with metastasis. Thus, these cancer prognostic metastasis factors and TFs of cancer stem cells, except for E-cadherin and HPRT1 , can be used as reliable metastasis factors for canine MGT and therapeutic strategy.
2.Induced neural stem cells from human patient-derived fibroblasts attenuate neurodegeneration in Niemann-Pick type C mice
Saetbyul HONG ; Seung-Eun LEE ; Insung KANG ; Jehoon YANG ; Hunnyun KIM ; Jeyun KIM ; Kyung-Sun KANG
Journal of Veterinary Science 2021;22(1):e7-
Background:
Niemann-Pick disease type C (NPC) is caused by the mutation of NPC genes, which leads to the abnormal accumulation of unesterified cholesterol and glycolipids in lysosomes. This autosomal recessive disease is characterized by liver dysfunction, hepatosplenomegaly, and progressive neurodegeneration. Recently, the application of induced neural stem cells (iNSCs), converted from fibroblasts using specific transcription factors, to repair degenerated lesions has been considered a novel therapy.
Objectives:
The therapeutic effects on NPC by human iNSCs generated by our research group have not yet been studied in vivo; in this study, we investigate those effects.
Methods:
We used an NPC mouse model to efficiently evaluate the therapeutic effect of iNSCs, because neurodegeneration progress is rapid in NPC. In addition, application of human iNSCs from NPC patient-derived fibroblasts in an NPC model in vivo can give insight into the clinical usefulness of iNSC treatment. The iNSCs, generated from NPC patientderived fibroblasts using the SOX2 and HMGA2 reprogramming factors, were transplanted by intracerebral injection into NPC mice.
Results:
Transplantation of iNSCs showed positive results in survival and body weight change in vivo. Additionally, iNSC-treated mice showed improved learning and memory in behavior test results. Furthermore, through magnetic resonance imaging and histopathological assessments, we observed delayed neurodegeneration in NPC mouse brains.
Conclusions
iNSCs converted from patient-derived fibroblasts can become another choice of treatment for neurodegenerative diseases such as NPC.
3.Metastasis prognostic factors and cancer stem cell-related transcription factors associated with metastasis induction in canine metastatic mammary gland tumors
Saetbyul KIM ; Eunyeong BOK ; Sangyeob LEE ; Hyeon-Jeong LEE ; Yongho CHOE ; Na-Hyun KIM ; Won-Jae LEE ; Gyu-Jin RHO ; Sung-Lim LEE
Journal of Veterinary Science 2021;22(5):e62-
Background:
Canine mammary gland tumor (MGT) is the most common cancer in aged female dogs. Although it's important to identify reliable metastasis or prognostic factors by evaluating related to cell division, adhesion, and cancer stem cell-related transcription factor (TF) in metastasis-induced canine MGT, but there are limited studies.
Objectives:
We aimed to identify metastasis prognostic factors and cancer stem cell-TFs in canine MGTs.
Methods:
Age-matched female dogs diagnosed with MGT only were classified into metastatic and non-metastatic groups by histopathological staining of MGT tissues. The mRNA levels of cancer prognostic metastasis molecular factors (E-cadherin, ICAM-1, PRR14, VEGF, HPRT1, RPL4 and hnRNP H ) and cancer stem cell-related TFs (Oct4, Sox2, and Nanog ) were compared between metastatic and non-metastatic canine MGT tissues using qRT-PCR analysis.
Results:
The mRNA levels of ICAM-1, PRR14, VEGF, hnRNP H, Oct4, Sox2, and Nanog in metastatic MGT group were significantly higher than those in non-metastatic MGT group. However, mRNA level of RPL4 was significantly lower in metastatic MGT group. Loss of E-cadherin and HPRT1 was observed in the metastatic MGT group but it was not significant.
Conclusions
Consistent expression patterns of all metastasis-related factors showing elevation in ICAM-1, PRR14, VEGF, hnRNP H, Oct4, Sox2, and Nanog, but decreases in RPL4 levels occurred in canine MGT tissues, which was associated with metastasis. Thus, these cancer prognostic metastasis factors and TFs of cancer stem cells, except for E-cadherin and HPRT1 , can be used as reliable metastasis factors for canine MGT and therapeutic strategy.