Partial hepatectomy enhances the growth of CC531 rat colorectal cancer cells both in vitro and in vivo

Borja Herrero De La Parte,Teodoro Palomares,Ignacio García-Alonso,Iñaki Diaz-Sanz,Mikel González-Arribas

doi:10.1038/s41598-021-85082-z

Borja Herrero De La Parte, Teodoro Palomares + Show 3 more

Open Access

https://doi.org/10.1038/s41598-021-85082-z

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Abstract

Partial hepatectomy (PHx) is the gold standard for the treatment of colorectal cancer liver metastases. However, after removing a substantial amount of hepatic tissue, growth factors are released to induce liver regeneration, which may promote the proliferation of liver micrometastases or circulating tumour cells still present in the patient. The aim of this study is to assess the effect of PHx on the growth of liver metastases induced by intrasplenic cell inoculation as well as on in vitro proliferation of the same cancer cell line. Liver tumours were induced in 18 WAG/RijHsd male rats, by seeding 250,000 syngeneic colorectal cancer cells (CC531) into the spleen. The left lateral lobe of the liver was mobilized and in half of the animals it was removed to achieve a 40% hepatectomy. Twenty-eight days after tumour induction, the animals were sacrificed and the liver was removed and sliced to assess the relative tumour surface area (RTSA%). CC531 cells were cultured in presence of foetal calf serum, non-hepatectomised (NRS) or hepatectomized rat serum (HRS), and their proliferation rate at 24, 48, and 72 h was measured. RTSA% was significantly higher in animals which had undergone PHx than in the controls (non-hepatectomised) (46.98 ± 8.76% vs. 18.73 ± 5.65%; p < 0.05). Analysing each lobe separately, this difference in favour of hepatectomized animals was relevant and statistically significant in the paramedian and caudate lobes. But in the right lobe the difference was scarce and not significant. In vitro, 2.5% HRS achieved stronger proliferative rates than the control cultures (10% FCS) or their equivalent of NRS. In this experimental model, a parallelism has been shown between the effect of PHx on the growth of colorectal cancer cells in the liver and the effect of the serum on those cells in vitro.

Highlights

Partial hepatectomy (PHx) is the gold standard for the treatment of colorectal cancer liver metastases
In order to select appropriate control conditions, first of all, we analysed the effect of adding serum obtained from normal rats (NRS) to CC531 cell cultures, comparing their growth rate at 72 h with that of cultures enriched with conventional 10% foetal calf serum (FCS)
Though no differences were observed during the first 48 h (Fig. 1), looking at cell counts on the third day, none of the cultures enriched with NRS reached the cell numbers obtained with FCS, being the culture with the lowest concentration of NRS (5%) the one that was closest to the control

Summary

Introduction

Partial hepatectomy (PHx) is the gold standard for the treatment of colorectal cancer liver metastases. The aim of this study is to assess the effect of PHx on the growth of liver metastases induced by intrasplenic cell inoculation as well as on in vitro proliferation of the same cancer cell line. 2.5% HRS achieved stronger proliferative rates than the control cultures (10% FCS) or their equivalent of NRS. In this experimental model, a parallelism has been shown between the effect of PHx on the growth of colorectal cancer cells in the liver and the effect of the serum on those cells in vitro. Some studies suggest that these tumour microimplants or some circulating tumour cells may be in a kind of “dormant state” which is suddenly abandoned to begin rapid g rowth[16,17]

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