Increased growth of colorectal liver metastasis following partial hepatectomy

Abstract

Nearly 50 % of colorectal cancer (CRC) patients develop liver metastases with liver resection being the only option to cure patients. Residual micrometastases or circulating tumor cells are considered a cause of tumor relapse. This work investigates the influence of partial hepatectomy (PH) on the growth and molecular composition of CRC liver metastasis in a syngeneic rat model. One million CC531 colorectal tumor cells were implanted via the portal vein in WAG/Rij rats followed by a 30 % PH a day later. Control groups either received tumor cells followed by a sham-operation or were injected with a buffer solution followed by PH. Animals were examined with magnetic resonance imaging (MRI) and liver tissues were processed for immunolabeling and PCR analysis. One-third PH was associated with an almost threefold increase in relative tumor mass (MRI volumetry: 2.8-fold and transcript levels of CD44: 2.3-fold). Expression of molecular markers for invasiveness and aggressiveness (CD49f, CXCR4, Axin2 and c-met) was increased following PH, however with no significant differences when referring to the relative expression levels (relating to tumor mass). Liver metastases demonstrated a significantly higher proliferation rate (Ki67) 2 weeks following PH and cell divisions also increased in the surrounding liver tissue. Following PH, the stimulated growth of metastases clearly exceeded the compensation in liver volume with long-lasting proliferative effects. However, the distinct tumor composition was not influenced by liver regeneration. Future investigations should focus on the inhibition of cell cycle (i.e. systemic therapy strategies, irradiation) to hinder liver regeneration and therefore restrain tumor growth.

Association between Ki67 Index and Clinicopathological Features in Colorectal Cancer

“…It was reported that liver metastases of CRC demonstrated a significantly higher Ki67 labeling index (Ki67-Li) [7]. Ki67 expression was found to be significantly higher in tumor tissues than in peritumoral tissues, and Ki67 levels were significantly associated with lymph node metastasis and poor prognosis of CRC [8].…”

The Differences of c-Met Expression Between AFP-Producing Gastric Cancer and Common Gastric Cancer

“…10 Krause et al, proved that the c-Met pathway is related to liver metastasis of colon cancer, and the higher frequency of c-Met expression leads to a higher recurrence rate after resection of liver metastatic cancer. 11 The positive rate of c-Met in common gastric cancers ranges from 18%-71.1%. The gene amplification of c-Met is correlated with cancer stage, and c-Met is found to be overexpressed in gastric cancers with deeper invasion and distant metastasis.…”

Increased kinetic growth rate during late phase liver regeneration impacts the risk of tumor recurrence after colorectal liver metastases resection

“…5,11 In fact, it has been suggested that growth factors secreted during liver regeneration may have a greater stimulatory effect on tumor cells than on hepatocytes. [27][28][29][30] The current study is important because we assessed the impact of the extent of regeneration on long-term oncologic outcomes following liver resection in the clinical setting. The data demonstrated that the liver regeneration-tumor stimulation paradigm, which had previously been proposed in preclinical experimental studies, was also associated with recurrence among patients with CRLM in the clinical setting.…”