New Emerging Patient-derived Circulating Tumor Cells (CTCs) as Promising Tools for Cancer Research

Circulating tumor cells (CTCs) play a significant role in understanding the mechanisms of cancer biology and, more specifically, metastatic tumors. CTCs are cells from a primary tumor that break away to circulate through the bloodstream and metastasize in other areas of the body. CTCs have been proposed as valuable tools for the early diagnosis, monitoring, and identification of tumor progression as they provide possible new therapeutic targets. However, CTCs have relatively low numbers in the bloodstream as compared to other cell types, which makes isolating and establishing a CTC line difficult. Further, while researchers are able to identify and isolate these cells with new techniques, there is a lack of established CTC lines that are widely available to the research community for basic mechanism studies and translational research. 

Collaborating with leading research institutions, ATCC is putting effort into developing methods and protocols for the expansion and characterization of human CTC lines isolated from clinical patient samples. In this study, we demonstrated the propagation and characterization of a melanoma CTC line MEL 167 (ATCC CRL-3651), which originated from metastatic melanoma patient sample. 

Here, we evaluated the MEL 167 cell line at the genetic and protein levels and assessed its bio-functional aspects. Genetic profiling of MEL 167 by sequencing analysis revealed various oncogenes that may enable the progression of metastasis. Immunofluorescence staining was performed to assess the presence of a distinct melanoma molecular marker panel. Additionally, the drug response to BRAF-inhibitors of MEL 167 was evaluated. We also compared the drug profile of this new CTC model to the established melanoma cell line model A375 (ATCC CRL-1619) and two other drug-resistant melanoma cell lines that were created through CRISPR gene editing. We found that melanoma metastases are highly malignant with a low response rate to immunotherapies and high potential for relapse from drug-resistance stemming from tumor heterogeneity. As a newly emerging CTC model, MEL 167 (ATCC CRL-3651) offers a promising tool for pre-clinical studies and for evaluating CTCs in the early diagnosis and monitoring of metastatic melanoma.