Comparison of implantation sites for the development of peritoneal metastasis in a colorectal cancer mouse model using non-invasive bioluminescence imaging

Abstract

The development of cancer mouse models is still needed for the identification and preclinical validation of novel therapeutic targets in colorectal cancer, which is the third leading cause of cancer-related deaths in Europe. The purpose of this study was to determine the most accurate tumour cell injection method to obtain suitable peritoneal metastasis (PM) for subsequent therapeutic treatments. Here, we grafted murine colon carcinoma CT-26 cells expressing luciferase into immunocompetent BALB-c mice by intravenous injection (IV group), subcutaneous injection (SC group), intraperitoneal injection after peritoneal scratching (A group) or intraperitoneal injection alone (IP group). Tumour growth was monitored by bioluminescence during the first 15 days post-grafting. The peritoneal carcinomatosis index was evaluated macroscopically, histology, immunohistochemistry and multiphoton microscopy were performed in peritoneal tumour tissue. Upon implantation, no tumour growth was observed in the IV group, similar to the non-injected group. Both the IP and SC groups showed intermediate growth rates, but the SC group produced only a single subcutaneous nodule. The A group exhibited the highest tumour growth at 15 days post-surgery. Anatomic and histologic analyses corroborated the existence of various tumour nodules, and multiphoton microscopy was used to evaluate tumour fibrosis-infiltrating cells in a non-pathologic peritoneum. In conclusion, limited PM was obtained by IP injection, whereas IP injection after peritoneal scratching led to an extensive PM murine model for evaluating new therapeutics.

CD31 and D2-40 Contribute to Peritoneal Metastasis of Colorectal Cancer by Promoting Epithelial-Mesenchymal Transition

“…The PCI has been employed by surgeons as a classic quantitative method to evaluate the extent of peritoneal cancer in the peritoneal cavity, and the PCI score tightly correlates with the patient’s prognosis, 20 and was also employed in this study to assess peritoneal metastasis in a mouse model of CRPM. 16 Simply put, PCI of SW480 cells with CD31+D2-40 overexpression was significantly higher than the control ( Fig. 7A ), while that of S5 cells with CD31+D2-40 KD was apparently lower than its respective control as well ( Fig.…”

“…Importantly, to verify the roles of CD31 and D2-40 in CRPM, a recently reported mouse model of CRPM was utilized, in which CRC cells were directly grafted into the peritoneal cavity. 16 As reported, the major quantitative endpoint to evaluate degree of CRPM, PCI was assessed in our experimental mice with the peritoneal cavity grafts. The results confirmed much severe extent of peritoneal metastasis with CD31 and D2-40 overexpression, which was otherwise attenuated by CD31+D2-40 KD.…”

“…CRPM in mouse model was established according to previous methods. 16 The 8 to 12 weeks old BALB/cByJ mice were randomly assigned into each group, with eight mice per group. Briefly, the mouse was anesthetized through an intraperitoneal injection of ketamine/xylazine mixture and the skin over the abdomen was disinfected.…”

Mouse Models of Peritoneal Carcinomatosis to Develop Clinical Applications

“…A wide repertoire of syngeneic rodent cell lines has been studied in different PCa model research contexts. Among the most common cell lines to develop peritoneal metastasis in syngeneic mouse models are MC38 and CT26 (colon adenocarcinoma cell lines from the inbred C57BL/6 and Balb/c strains, respectively) [ 27 , 28 , 29 , 30 , 31 , 32 ], ID8 (an epithelial ovarian cancer cell line from C57BL/6) [ 33 , 34 , 35 , 36 ], YTN16 (a gastric cancer cell line from C57BL/6) [ 37 , 38 ], and Panc02 (a pancreatic adenocarcinoma epithelial cell line from C57BL/6) [ 25 , 39 , 40 , 41 ]. Some studies have also used the melanoma cell line B16.F10 for peritoneal carcinomatosis as an alternative albeit unreal model, in part as it offers the advantages of the implants being highly detectable due to melanin secretion and the aggressive progression of such tumors [ 42 , 43 , 44 ].…”

CD244+ polymorphonuclear myeloid‑derived suppressor cells reflect the status of peritoneal dissemination in a colon cancer mouse model

“…Therefore, we concluded that detailed immunological evaluation of PD nodules was difficult to conduct. However, other investigators have reported that immune cells are detectable and reflect immune responses and treatment effects (37,38). The differences are that the number of tumor cells used in these studies was much smaller than in our fast-growing PD model.…”