Abstract
Cyclooxygenase 2 (COX2) has been implicated in cancer development and metastasis. We have identified several COX2-regulated inflammation-related genes in human colorectal cancer cells and shown that some of them play important roles in tumor progression. In this work, we have studied the COX2-regulated genes in the mouse colorectal cancer cell line CT26, to find that many are also regulated by COX2 over-expression. On the other hand, we generated a CT26 cell line expressing Gfp and Luciferase, to study tumor growth and metastasis in immunocompetent Balb/c mice. We then collected solid tissue, and blood samples, from healthy and tumor-bearing mice. Using the Parsortix® cell separation system and taking advantage of the fact that the tumor cells expressed Gfp, we were able to identify circulating tumor cells (CTCs) in some of the mice. We compared the mRNA expression levels of Ptgs2 and effector genes in the samples obtained from tumor-bearing or healthy mice, namely, tumor or healthy colon, Ficoll purified buffy coat, and Parsortix-isolated cells to find different patterns between healthy, tumor-bearing mice with or without CTCs. Although for genes like Il15 we did not observe any difference between healthy and tumor-bearing mice in Ficoll or Parsortix samples; others, such as Egr1, Zc3h12a, Klf4, or Nfat5, allowed distinguishing for cancer or CTC presence. Gene expression analysis in Ficoll or Parsortix processed samples, after liquid biopsy, may offer valuable diagnostic and prognostic information and thus should be further studied.
Highlights
Colorectal cancer (CRC) is the second cause of cancer death in the developed countries
Cyclooxygenase 2 (COX2) overexpression has been associated with colorectal cancer progression and metastasis, it is upregulated in tumors vs. normal colon tissue and we have shown that PTGS2 is up-regulated in human xenografts in nude mice (Stamatakis et al, 2015)
We sought to investigate the mRNA levels of Ptgs2 in our mouse model of colon cancer, CT26 cells-Balb/c mice, as well as those of the group of COX2 effector genes we identified in human colon cancer
Summary
Colorectal cancer (CRC) is the second cause of cancer death in the developed countries. A small decrease in the death numbers caused by this type of cancer has been achieved, mainly due to prevention and early screening (Siegel et al, 2020). Circulating tumor cell (CTC) enumeration is used as a prognostic tool in different cancer types, among them, metastatic colorectal cancer (Sastre et al, 2012; Sotelo et al, 2015). The CTCs have been found to be very heterogenous, varying in surface marker expression, which reduces the value of FDA-approved tools, such as the CellSearch system (Gervasoni et al, 2011; Raimondi et al, 2014). Taking advantage of the physical characteristics of the CTCs, rather than the specific surface or expression markers, to isolate them, the Parsortix system has been able to isolate CTCs from a great variety of tumors and patients and it has been used in preclinical models (Kitz et al, 2018; Obermayr et al, 2018; Obermayr et al, 2019)
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