The VAR2CSA malaria protein efficiently retrieves circulating tumor cells in an EpCAM-independent manner

Agerbæk, Mette Ø.; Bang-Christensen, Sara R.; Yang, Ming-Hsin; Clausen, Thomas; Pereira, Marina Ayres; Sharma, Shreya; Ditlev, Sisse B.; Nielsen, Morten A.; Choudhary, Swati; Gustavsson, Tobias; Sorensen, Poul H.; Meyer, Tim; Propper, David; Shamash, Jonathan; Theander, Thor G.; Aicher, Alexandra; Daugaard, Mads; Heeschen, Christopher; Salanti, Ali

doi:10.1038/s41467-018-05793-2

Cited by 127 publications

(115 citation statements)

References 59 publications

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“…In the second step, putative CTCs are further stained and identified using anti-cytokeratin antibodies while contaminant white blood cells (WBCs) are identified by means of CD45 staining. Currently, CellSearch is the only CTC isolation device that is approved by the US Food and Drug Administration (FDA) [5], although "sister" antigen-based CTC isolation technologies are continuously emerging [6,7]. CellSearch has been validated in large patient cohorts, and its main use concerns CTC enumeration to identify high-risk patients with decreased progression-free survival and decreased overall survival in breast, prostate, and colorectal cancers [5,8].…”

Section: Ctc Isolation Technologiesmentioning

confidence: 99%

Tracking cancer progression: from circulating tumor cells to metastasis

2020

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The analysis of circulating tumor cells (CTCs) is an outstanding tool to provide insights into the biology of metastatic cancers, to monitor disease progression and with potential for use in liquid biopsy-based personalized cancer treatment. These goals are ambitious, yet recent studies are already allowing a sharper understanding of the strengths, challenges, and opportunities provided by liquid biopsy approaches. For instance, through single-cellresolution genomics and transcriptomics, it is becoming increasingly clear that CTCs are heterogeneous at multiple levels and that only a fraction of them is capable of initiating metastasis. It also appears that CTCs adopt multiple ways to enhance their metastatic potential, including homotypic clustering and heterotypic interactions with immune and stromal cells. On the clinical side, both CTC enumeration and molecular analysis may provide new means to monitor cancer progression and to take individualized treatment decisions, but their use for early cancer detection appears to be challenging compared to that of other tumor derivatives such as circulating tumor DNA. In this review, we summarize current data on CTC biology and CTC-based clinical applications that are likely to impact our understanding of the metastatic process and to influence the clinical management of patients with metastatic cancer, including new prospects that may favor the implementation of precision medicine. Publisher's NoteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Section: Ctc Isolation Technologiesmentioning

confidence: 99%

Tracking cancer progression: from circulating tumor cells to metastasis

2020

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“…Overall, so far there is no hard evidence for the prognostic advantage of the EpCAM-independent approaches in BC. Interestingly, there might be another way to bypass the problems with EpCAM-dependent isolation: finding some other, more universally expressed marker, like, for example the malaria protein VAR2CSA [108].…”

Section: Current Technical Limitations In Ctc Clinical Researchmentioning

confidence: 99%

Circulating Tumor Cells in Early and Advanced Breast Cancer; Biology and Prognostic Value

Fabisiewicz

Szostakowska-Rodzoś

Żaczek

et al. 2020

IJMS

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Breast cancer metastasis is the leading cause of cancer deaths in women and is difficult to combat due to the long periods in which disseminated cells retain a potential to be re-activated and start the relapse. Assessing the number and molecular profile of circulating tumor cells (CTCs) in breast cancer patients, especially in early breast cancer, should help in identifying the possibility of relapse in time for therapeutic intervention to prevent or delay recurrence. While metastatic breast cancer is considered incurable, molecular analysis of CTCs still have a potential to define particular susceptibilities of the cells representing the current tumor burden, which may differ considerably from the cells of the primary tumor, and offer more tailored therapy to the patients. In this review we inspect the routes to metastasis and how they can be linked to specific features of CTCs, how CTC analysis may be used in therapy, and what is the current status of the research and efforts to include CTC analysis in clinical practice.There are two main hypotheses describing cancer dissemination: linear progression, according to which, metastatic potential is gained gradually, and the whole process proceeds in steps and needs time, and parallel progression, according to which dissemination takes place early on, even before clinical manifestation of the tumor [6,7] (Figure 1). In the linear progression model, the evolving primary tumor gives rise to metastases due to increasingly aggressive and invasive phenotypes of the subclones of tumor cells. This model is in agreement with the postulated role of the epithelial-to-mesenchymal transition (EMT) in cancer and assumes active degradation of the stroma and migration into blood vessels by the motile, invasive single cells that broke loose from the epithelial monolayer. In contrast to that, parallel progression postulates intravasation by passive shedding, which may take place shortly after the angiogenic switch, occurring during the early, pre-invasive stage of tumor development [8,9].

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“…Targeting oncofetal chondroitin sulfate (ofCS) by the malarial recombinant VAR2CSA (rVAR2) protein might hold potential as a near-universal CTC-targeting agent as it binds to cancer cells independently of tumor origin. Furthermore, we have previously shown that rVAR2 binding to cancer cells is unaffected by cell plasticity such as epithelial-to-mesenchymal transition (EMT) [26]. This is an important trait since EMT is indicative of increased metastatic capacity of CTCs [31].…”

Section: Discussionmentioning

confidence: 99%

“…Our initial CTC studies have shown promise for an rVAR2-based capture method, yet several technical aspects of the method remain unexplored. Previous clinical CTC data was based on the DBL1-ID2a (121 kDa) rVAR2 construct, but for this optimization study we also included the smaller ID1-ID2a (70 kDa) construct (Figure 1a) [26]. Both recombinant forms of rVAR2 are well defined in terms of ofCS specificity and affinity [19].…”

Section: Recombinant Var2csa Can Be Efficiently Coupled To Sera-mag Bmentioning

confidence: 99%

Optimization of rVAR2-Based Isolation of Cancer Cells in Blood for Building a Robust Assay for Clinical Detection of Circulating Tumor Cells

Sand

Petersen

Bang-Christensen

et al. 2020

IJMS

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Early detection and monitoring of cancer progression is key to successful treatment. Therefore, much research is invested in developing technologies, enabling effective and valuable use of non-invasive liquid biopsies. This includes the detection and analysis of circulating tumor cells (CTCs) from blood samples. Recombinant malaria protein VAR2CSA (rVAR2) binds a unique chondroitin sulfate modification present on the vast majority of cancers and thereby holds promise as a near-universal tumor cell-targeting reagent to isolate CTCs from complex blood samples. This study describes a technical approach for optimizing the coupling of rVAR2 to magnetic beads and the development of a CTC isolation platform targeting a range of different cancer cell lines. We investigate both direct and indirect approaches for rVAR2-mediated bead retrieval of cancer cells and conclude that an indirect capture approach is most effective for rVAR2-based cancer cell retrieval.

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The VAR2CSA malaria protein efficiently retrieves circulating tumor cells in an EpCAM-independent manner

Cited by 127 publications

References 59 publications

Tracking cancer progression: from circulating tumor cells to metastasis

Tracking cancer progression: from circulating tumor cells to metastasis

Circulating Tumor Cells in Early and Advanced Breast Cancer; Biology and Prognostic Value

Optimization of rVAR2-Based Isolation of Cancer Cells in Blood for Building a Robust Assay for Clinical Detection of Circulating Tumor Cells

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