Establishment of various biliary tract carcinoma cell lines and xenograft models for appropriate preclinical studies

Abstract

We recently reported several driver genes of biliary tract carcinoma (BTC) that are known to play important roles in oncogenesis and disease progression. Although the need for developing novel therapeutic strategies is increasing, there are very few BTC cell lines and xenograft models currently available for conducting preclinical studies. Using a total of 88 surgical BTC specimens and 536 immunodeficient mice, 28 xenograft models and 13 new BTC cell lines, including subtypes, were established. Some of our cell lines were found to be resistant to gemcitabine, which is currently the first choice of treatment, thereby allowing highly practical preclinical studies to be conducted. Using the aforementioned cell lines and xenograft models and a clinical pathological database of patients undergoing BTC resection, we can establish a preclinical study system and appropriate parameters for drug efficacy studies to explore new biomarkers for practical applications in the future studies.

Biliary tract cancer patient-derived xenografts: Surgeon impact on individualized medicine

“…22 While there have been descriptions of the establishment of a limited number of biliary tract cancer PDX models, here we describe the largest biliary tract PDX library reported to date. [23][24][25][26][27]…”

Synergistic and Pharmacotherapeutic Effects of Gemcitabine and Cisplatin Combined Administration on Biliary Tract Cancer Cell Lines

“…Of these cell lines, 13 were our established cell lines: five were derived from extrahepatic BTC (NCC-BD1, NCC-BD2, NCC-BD3, NCC-BD4-1, and NCC-BD4-2) and eight were derived from intrahepatic BTC (NCC-CC1, NCC-CC3-1, NCC-CC3-2, NCC-CC4-1, NCC-CC4-2, NCC-CC4-3 (NCC-CC5), NCC-CC6-1, and NCC-CC6-2). Further information regarding these cell lines is presented in Table 1 [15,16]. Of the other four cell lines, three (HuCCT1, TKKK, and TGBC24TKB) were obtained from Riken Bio Resource Center (Tsukuba, Japan) and one (OZ) was obtained from the Japanese Collection of Research Bioresources (Osaka, Japan).…”

“…The data for GEM administration for our 13 established cell lines were obtained from our previous report [15,16]. For HuCCT1, TKKK, OZ, and TGBC24TKB, the same concentrations in the range 0–100 μM (0, 0.0001, 0.00033, 0.00067, 0.001, 0.0033, 0.0067, 0.01, 0.033, 0.067, 0.1, 0.33, 0.67, 1, 3.3, 6.7, 10, 33, 67, and 100 μM) as those in our previous reports were used [15,16]. The CDDP concentrations for addition to all cell lines were also set in the range 0–100 μM (0, 0.001, 0.01, 0.1, 1, 10, 20, 30, 50, 75, and 100 μM).…”

“…However, as far as we know, there have been no detailed studies on the pharmacotherapeutic activity, synergistic effect, and plasma clearance of GC. In our previous work, we established a number of BTC cell lines and performed in vitro sensitivity studies for several anticancer drugs, including GEM [15,16]. Some of our BTC cell lines showed resistance to GEM.…”

Experimental models to unravel the molecular pathogenesis, cell of origin and stem cell properties of cholangiocarcinoma

“…Published CCA cell lines up to 2013 were reviewed by Zach et al 6 Several others have been established since then. [7][8][9][10][11] CCA cell lines used most frequently include iCCA cell lines RBE 12 and HuCC-T1, 13 pCCA cell lines KKU-100 14 and QBC939 15,16 and dCCA cell line TFK-1. 17 Key characteristics of these commonly used cell lines are portrayed in Table 2.…”