Colonoscopy-Based Intramucosal Transplantation of Cancer Cells for Mouse Modeling of Colon Cancer and Lung Metastasis

Abstract

The conventional orthotopic/xenograft models or genetically engineered murine models of colon cancer (CRC) are limited in their scope for a true understanding of tumor growth, progression and eventual metastasis in its natural microenvironment. In the currently used murine models of CRC metastasis, the metastasis occurs primarily in the liver, though lung metastasis accounts for a significant proportion of CRC metastasis. There is an urgent need for a murine model of CRC, which not only allows tumor progression in the colonic mucosa but also metastasis of the lung. The authors describe a minimally invasive murine model of colon cancer progression that may be ideal for a wide range of applications, including evaluating gene function, microenvironment, cancer metastasis and therapeutic translational research.

A natural halogenated fluoride adenosine analog 5′‐fluorodeoxy adenosine induced anticolon cancer activity in vivo and in vitro

“…Among malignant tumors, colon cancer is the third most common malignant tumor affecting men and women 33 . Metastasis is the cause for up to 90% of cancer‐related deaths, 34 but there are few effective drugs specifically targeting metastatic or metastatic potential cells 35 .…”

“…Among malignant tumors, colon cancer is the third most common malignant tumor affecting men and women. 33 Metastasis is the cause for up to 90% of cancer-related deaths, 34 but there are few effective drugs specifically targeting metastatic or metastatic potential cells. 35 As previous reported, ADO induced DNA damage, apoptosis, autophagy, cell cycle arrest, antiangiogenesis, and antimetastatic pathways in cancer cells.…”

Pyrroline-5-Carboxylate Reductase-2 Promotes Colorectal Carcinogenesis by Modulating Microtubule-Associated Serine/Threonine Kinase-like/Wnt/β-Catenin Signaling

“…Colonoscopy-guided injection of CRC cells into the colonic mucosa was performed as previously described by our laboratory [29]. Control and PYCR2-KO HCT116 cells (10 6 cells/50 µL) were used for intramucosal transplantation into the colon walls of nude mice (n = 4/group) by using a small-animal colonoscope (COLOVIEW; Karl-Storz, Tuttlingen, Germany).…”

“…At the study termination, tumors in mice injected with PYCR2-KD cells were significantly smaller in size (p = 0.0048) and weight (p = 0.0019) relative to the tumors from mice injected with the control cells (Figure 4(Bii,Biii)). To further determine the role of PYCR2 in colon carcinogenesis in a true colonic microenvironment, we used an orthotopic xenograft model recently described by our lab, where cancer cells are transplanted into the colonic wall to generate tumors [29]. A colonoscopy-guided intramucosal cell transplantation was performed on athymic/nude mice (8 weeks old).…”