Rare osteosarcoma cell subpopulation protein array and profiling using imaging mass cytometry and bioinformatics analysis

Abstract

Background Single rare cell characterization represents a new scientific front in personalized therapy. Imaging mass cytometry (IMC) may be able to address all these questions by combining the power of MS-CyTOF and microscopy. Methods We have investigated this IMC method using < 100 to up to 1000 cells from human sarcoma tumor cell lines by incorporating bioinformatics-based t-Distributed Stochastic Neighbor Embedding (t-SNE) analysis of highly multiplexed IMC imaging data. We tested this process on osteosarcoma cell lines TC71, OHS as well as osteosarcoma patient-derived xenograft (PDX) cell lines M31, M36, and M60. We also validated our analysis using sarcoma patient-derived CTCs. Results We successfully identified heterogeneity within individual tumor cell lines, the same PDX cells, and the CTCs from the same patient by detecting multiple protein targets and protein localization. Overall, these data reveal that our t-SNE-based approach can not only identify rare cells within the same cell line or cell population, but also discriminate amongst varied groups to detect similarities and differences. Conclusions This method helps us make greater inroads towards generating patient-specific CTC fingerprinting that could provide an accurate tumor status from a minimally-invasive liquid biopsy.

Enhancing clinical potential of liquid biopsy through a multi-omic approach: A systematic review

“…Recently, FC-based technologies have been used and adapted to detect multiple markers at a single cell level too. In this regard, CTCs from osteosarcoma patient blood samples were characterized by Shulin Li’s research group a couple of years ago ( Batth et al, 2020 ). After having isolated CTCs for their positivity to vimentin and negativity to CD45, a multiplex labeling using antibodies conjugated to metal ions revealed the presence of 18 different markers simultaneously.…”

Canine and murine models of osteosarcoma

“…88,117,124,126 Cell lines can also be generated from PDXs and are easy to cryopreserve and store for later applications. 9,43,56,57,66,94,160 Interestingly, some cell lines are reported to carry specific drug resistance to the treatment to which the original tumor was exposed, suggesting that this may provide an important model to study treatment resistance, test novel therapeutic agents, or investigate combination therapies.…”

“…98,106,121 Osteoblastic is the most common subtype in the dog; however, similar to human tumors, 77 many canine OS are heterogenous and contain multiple histologic patterns (Figs. [8][9][10][11][12][13][14][15]. 121 This tumor heterogeneity may complicate the prognostic value of histopathology in canine osteosarcomas.…”

Application of High-Throughput Imaging Mass Cytometry Hyperion in Cancer Research

“…( 31 ) or osteosarcoma by Batth et al. ( 32 ). Applications of IMC to deeply phenotype cancer cell lines have been also reported as the work on breast cancer cell lines by Bouzekri et al.…”