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An Orthotopic Model of Serous Ovarian Cancer in Immunocompetent Mice for in vivo Tumor Imaging and Monitoring of Tumor Immune Responses
Published on: November 28, 2010
Biological characteristics of spontaneous ovarian cancer in Microtusfortis
Junkang Zhou1,2, Tianqiong He3,4, Yixin Wen3,4
1Department of Laboratory Animal Science, Xiangya School of Medicine, Central South University, Changsha 410013. zhou_junkang@163.com.
Objectives:
Wild-caught Microtus fortis (M. fortis) at the age of 9-15 months can develop epithelial ovarian cancers similar to human epithelial ovarian cancers under natural conditions during experimental animal breeding, but its pathological types and biological characteristics remain unclear. This study aims to analyze the biological characteristics of spontaneous ovarian cancer in M. fortis, intending to develop M. fortis as an animal model for human epithelial ovarian cancer.
Methods:
The female M. fortis (9-15 months old) with spontaneous ovarian cancer were selected as the experimental group, and healthy M. fortis from the same litter were selected as the control group. The ovarian pathological changes of the two groups were observed by dissection. Blood routine and biochemical indicators were measured by biochemical analysis. Hematoxylin and eosin (HE) staining was performed to observe the pathological changes in the ovarian cancer tissue of M. fortis. Immunohistochemical staining was used to detect the protein expression of common ovarian cancer markers, and real-time RT-PCR was used to analyze the transcription levels of ovarian cancer-related genes.
Results:
Spontaneous ovarian cancer in M. fortis mainly affects both ovaries, with tumors appearing solid or cystic. HE staining and histopathological analysis confirmed that the ovarian tumors originated from ovarian surface epithelium. Compared to the control group, the experimental group showed significantly decreased hemoglobin (P<0.01), hematocrit (P<0.05), albumin (P<0.05), and blood glucose levels (P<0.01), while lymphocyte percentage (P<0.05), monocyte percentage (P<0.05), cholesterol (P<0.01), and progesterone (P<0.01) levels were significantly increased. Expression of ovarian cancer-related genes, including ID3, CDC42, RHOA, RB1CC1, NF1, PIN1, MIB1, PDS5A, MCM7, and MLH1, was significantly downregulated (all P<0.05), while PAX8 gene expression was significantly upregulated (P<0.05). Immunohistochemical results showed that Wilms' tumor gene 1 (WT1) protein was mainly distributed throughout the cell, with significantly higher expression in ovarian cancer M. fortis. Tumor protein 53 (TP53) was expressed in both healthy and ovarian cancer M. fortis and was distributed throughout the cell. Hepatocyte nuclear factor 1 beta (HNF1B) and progesterone receptor (PR) protein were highly expressed in the ovarian tissue of healthy M. fortis but were significantly reduced in the ovarian cancer M. fortis, though both were located in the cytoplasm.
Conclusions:
Spontaneous ovarian cancer in M. fortis is serous ovarian cancer. Compared to healthy M. fortis, significant differences were observed in ovarian tissue morphology, biochemical indicators, ovarian cancer-related gene expression, and protein expression, which show similarity to the biological characteristics of human serous ovarian cancer. This suggests that M. fortis could be an ideal animal model for studying human serous ovarian cancer.
Insights
Spontaneous ovarian cancer in Microtus fortis (M. fortis) closely resembles human serous ovarian cancer. This study highlights M. fortis as a promising animal model for investigating human ovarian cancer biology and developing new treatments.
Area of Science:
- Oncology
- Comparative Pathology
- Animal Models
Background:
- Wild-caught Microtus fortis (M. fortis) aged 9-15 months can naturally develop epithelial ovarian cancers.
- The pathological types and biological characteristics of spontaneous ovarian cancer in M. fortis require clarification.
- Understanding these characteristics is crucial for establishing M. fortis as a viable animal model for human ovarian cancer research.
Purpose of the Study:
- To analyze the biological characteristics of spontaneous ovarian cancer in M. fortis.
- To evaluate the potential of M. fortis as an animal model for human epithelial ovarian cancer.
- To compare pathological and molecular features with human serous ovarian cancer.
Main Methods:
- Selected female M. fortis (9-15 months) with spontaneous ovarian cancer (experimental group) and healthy littermates (control group).
- Performed gross dissection, hematoxylin and eosin (HE) staining, immunohistochemistry, and real-time RT-PCR.
- Analyzed blood routine, biochemical indicators, ovarian pathological changes, gene expression (e.g., ID3, PAX8), and protein markers (e.g., WT1, TP53).
Main Results:
- Ovarian tumors in M. fortis originated from the ovarian surface epithelium and were solid or cystic, affecting both ovaries.
- Significant differences observed in biochemical indicators, including decreased hemoglobin and albumin, and increased cholesterol and progesterone in the cancer group.
- Downregulation of key genes (ID3, CDC42, RHOA) and upregulation of PAX8 observed; WT1 protein expression increased, while HNF1B and PR protein expression decreased in cancer tissues.
Conclusions:
- Spontaneous ovarian cancer in M. fortis is histopathologically identified as serous ovarian cancer.
- Observed similarities in morphology, biochemical markers, gene expression, and protein profiles to human serous ovarian cancer.
- M. fortis represents a suitable and promising animal model for studying human serous ovarian cancer.
