Primary Cholangiocellular Carcinoma Cell Lines

Review Article

J Stem Cell Res Transplant. 2015;2(1): 1013.

Primary Cholangiocellular Carcinoma Cell Lines

Sebastian Zach*, Emrullah Birgin and Felix Rückert

Department of Surgery, Medical Faculty Mannheim, University of Heidelberg, Germany

*Corresponding author: Sebastian Zach, Department of Surgery Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-368167; Mannheim

Received: December 03, 2014; Accepted: January 18, 2015; Published: January 20, 2015


Cholangio Cellular Cancer (CCC) is a deadly disease and 5-year overall survival still is below 10%. To improve prognosis of patients with CCC, basic science is absolutely dependent on cell lines to elaborate new insights into pathological, diagnostic and therapeutic options. This is a systematic review about CCC cell lines described in literature to date. Different cell lines were established and characterized in the last 30 years. CCC cell lines can generally be classified into cell lines derived from intra hepatic CCC (iCCC), extra hepatic CCC (eCCC), perihilar CCC (Klatskin) and metastasis. The aim of this review is to give insights in the availability of cell lines and the possibilities that these cell lines might give to researchers focused on CCC.


Cholangio Cellular Carcinoma (CCC) is a malignancy arising from epithelial cells of the biliary tree. The first case of common bile duct cancer was described by Durand-Fardel in 1840 [1]. Depending on tumor location CCC are differentiated as intra hepatic or extra hepatic. The latter can be further classified as distal and perihilar. 60- 70% of CCC a rise at the hepatic bifurcation (perihilar) and were first reported by Klatskin in 1965[2]. Approximately 20-30% accounts for tumors in the distal common bile duct and 5-10% for the intra hepatic type [3]. Known risk factors for cholangiocarcinoma include primary sclerosing cholangitis [4], fibrocystic liver diseases (e.g. Caroli’s syndrome) [5], parasitic infection (e.g. Opisthorcis viverrini) [6], viral hepatitis and cirrhosis [7], intra hepatic biliary stones[8] and chemical carcinogen exposure (e.g. thorotrast [9], smoking and alcohol[10,11]).

The incidence rate of CCC varies widely, e.g. 1-2/100,000 in the USA and 96/100,000 in Thailand [12]. In general, in Western countries and Japan the incidence of extra hepatic CCC is higher than intrahepatic CCC, whereas in Eastern countries the opposite can be seen [13]. Epidemiologic studies indicate a global increase of incidence and mortality rate for iCCC with stable or decreasing rates for eCCC [14,15].

However, the current treatment options remain still insufficient with a 5-year overall survival rate of 5-15%. The only curative approach is surgical therapy with radical resection, but up to 80% of patients present with advanced disease initially [16].

To elaborate diagnostic and therapeutic options and improve the prognosis of patients basic science is absolutely fundamental. For this purpose, tumor cell lines are essential. Tumor cell lines are an important source of material for “omic” studies, and they allow functional studies that help to better understand tumor biology, especially molecular pathogenesis and pathophysiology [17,18].

However, the amount of cell lines derived from CCC is limited. The majority of research in CCC has been done with only two cell lines EGI-1 and TFK [19-21]. A disadvantage of a limited number of cell lines’ use is that these cells cannot sufficiently represent tumor heterogeneity of CCC. Cell lines are prone to genetic drift and shift that might alter the tumor genome in the course of time. Additionally, cell lines that are cultivated long-term are prone to be contaminated with rapid growing cell lines like HeLa cells. Due to this the establishment of new cell lines is beneficial [22]. The aim of the present review gives an overview on CCC cell lines available for researchers that focus on this tumor entity. We will discuss characteristics of these cell lines as well as origin of the cell lines, techniques and medias that were used to establish these CCC cell lines.

Overview on cholangiocarcinoma cell lines

In the 19th century, the concept of tissue culture was introduced by Wilhelm Roux. Since the first successful isolation of cell lines in the 60ties, several CCC cell lines were described in literature (Table 1).