Fate and characterization of circulating tumor cells in a NOD/SCID mouse model of human hepatocellular carcinoma

Abstract

There is much debate about the way in which epithelial tumors metastasize. It has been proposed that the bone marrow (BM) acts as a tumor cell reservoir. We injected human hepatocellular carcinoma (HCC) cells (Mahlavu cell line) into the livers, circulation or BM of NOD/SCID mice and circulating tumor cells were quantified. When injected under the Glisson capsule, a primary tumor developed and continuously yielded circulating tumor cells. Liver tumor removal led to a very low level of Mahlavu cells both in blood and BM 30 days later. When Mahlavu cells (cultured or from BM of primary mice femurs) were intravenously injected into mice, the number of cells in the bloodstream (BS) steadily decreased, whereas the BM was not significantly colonized. When Mahlavu cells were directly injected into one femur, the controlateral femur was not colonized. Microscopic analysis and a sensitive PCR assay (o1 Mahlavu cell/ nuclear cells) both failed to detect human tumor cells in other organs regardless of injection route. In conclusion, our model strongly supports the hypothesis that HCCs continuously release cells into the BS. However, in sharp contrast with the current hypothesis, the BM is not specifically colonized by tumor cells but could store them at a very low level.

Circulating tumor cells: advances in detection methods, biological issues, and clinical relevance

“…Interestingly, HCC cells that were injected directly into peripheral circulation or bone marrow did not colonize in the liver. As Scatton et al (2006) noted in the literature, circulating Mahlavu cells seemed to predict disease progression efficiently but not specifically to imply tumor recurrence, which could be explained by the genetically limited ability of Mahlavu cells in the formation of metastasis. Instead of using EpCAM-labeled magnetic beads, Xu et al (2011) enriched CTC via an asialoglycoprotein receptor-based magnetic separation assay in HCC patients.…”

Circulating Tumor Cells Measurements in Hepatocellular Carcinoma

“…Currently, there are few models of orthotopic implantation of human tumoral cells [180, 181]. An experimental model of human orthotopic HCC transplantation in NOD/SCID (nonobese diabetic/several compromise immunodeficient) mice allows to generate and to modulate CTC [180, 181]. In this mouse model, tumoral spreading is an early event during tumoral development and the number of CTC is directly correlated to the tumor size.…”

Chick embryo chorioallantoic membrane model systems to study and visualize human tumor cell metastasis

“…The size of aggressive tumors and time of their development also correlate with the appearance and increasing frequency of tumor cells in the circulation in mice (Allan et al 2005; Scatton et al 2006). High levels of intravasation exhibited by HT-hi/diss cells prompted us to attempt detection of circulating human tumor cells during spontaneous metastasis in the chick embryo.…”