Publications

[Impact factor; no. of citations in Google Scholar]

I. Tumor Surfaceome Mapping (TS-MAP) for tumor antigen identification in GBM

1. Bourseau-Guilmain E, Menard JA, Lindqvist E, Indira Chandran V, Christianson HC, Cerezo Magaña M, Lidfeldt J, Marko-Varga G, Welinder C, Belting M. Hypoxia regulates global membrane protein endocytosis through caveolin-1 in cancer cells. Nature Communications. 2016; 20: 11371-83.  *[17.7; 114]. Corresponding author. 

We develop the TS-MAP platform, showing that stress conditions modulate surfaceome turnover in cancer cells, providing opportunities for tumor specific drug delivery.

2. Governa V, Talbot H, Gonçalves de Oliveira K, Cerezo-Magaña M, Bång-Rudenstam A, Johansson MC, Månsson AS, Forsberg-Nilsson K, Marko-Varga G, Enríquez Pérez J, Darabi A, Malmström J, Bengzon J, Welinder C, Belting M. Landscape of surfaceome and endocytome in human glioma is divergent and depends on cellular spatial organization. Proceedings of the National Academy of Sciences USA. 2022; 119: e2114456119. Direct submission track. *[12.8; 10]. Corresponding author. 

We optimize the TS-MAP method for global profiling of surface proteins as targets for immunotherapies directly in GBM patient tissue and experimental 3D glioma models. Our findings indicate that the repertoire and variation of tumor antigens in patient tumors is significant, which emphasizes the importance of proteomic analyses for individualized treatment.

3. Gonçalves de Oliveira K, Bång Rudenstam A, Beyer S, Boukredine A, Talbot H, Governa V, Johansson MC, Månsson AS, Forsberg Nilsson K, Bengzon J, Malmström J, Welinder C, Belting M. Decoding of the surfaceome and endocytome in primary glioblastoma cells identifies potential target antigens in the hypoxic tumor niche. Acta Neuropathathologica Communications 2024; 12: 35. *[7.1; -]. Corresponding author.

We further develop the TS-MAP method to map surface antigens in the hypoxic tumor niche in GBM. We establish methods to target hypoxia-induced surface antigens with antibody-drug conjugates (ADCs). The study contributes with new insights into the poor correlation between mRNA and protein expression for membrane-associated surface antigens, thereby underscoring the importance of proteomics-based methods. 

II. Adaptive mechanisms of the hypoxic GBM niche – role for exosomes

We establish a dual role for exosomes as signalosomes and extracellular nutrients with importance for tumor cell adaptation in the hypoxic GBM niche. 

4. Kucharzewska P, Christianson HC, Welch JE, Svensson KJ, Fredlund E, Ringnér M, Mörgelin M, Bourseau-Guilmain E, Bengzon J, Belting M. Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development. Proceedings of the National Academy of Sciences USA. 2013; 110: 7312-7. Direct submission track. * [12.8; 992]. Corresponding author. 

In this highly cited paper, we show that exosomes from glioma patients serve as a novel, non-invasive biomarker, and that exosomes constitute a potentially targetable mediator of tumor development.

5. Christianson HC, Svensson KJ, van Kuppevelt TH, Li JP, Belting M. Cancer cell  exosomes depend on cell-surface heparan sulfate proteoglycans for their internalization and functional activity. Proceedings of the National Academy of Sciences USA. 2013; 110: 17380-5. Direct submission track. * [12.8; 960]. Corresponding author. 

In this highly cited paper, we identify heparan sulfate proteoglycan as a novel receptor and potential target for inhibition of exosome mediated glioma tumor development. 

6. Menard JA, Christianson HC, Kucharzewska P, Bourseau-Guilmain E, Svensson KJ, Lindqvist E, Chandran VI, Kjellén L, Welinder C, Bengzon J, Johansson MC, Belting M. Metastasis Stimulation by Hypoxia and Acidosis-Induced Extracellular Lipid Uptake Is Mediated by Proteoglycan Dependent Endocytosis. Cancer Research. 2016; 76: 4828-40. * [13.3; 103]. Corresponding author. 

We find that glioma tumors adapt to stress through increased recruitment of lipids, resulting in a lipid storing metabolic phenotype as a potentially targetable driver of tumor development. 

7. Offer S, Menard JA, Enríquez Pérez J, de Oliveira KG, Indira Chandran V, Johansson MC, Bång-Rudenstam A, Siesjö P, Ebbesson A, Hedenfalk I, Sundgren PC, Darabi A, Belting M. Extracellular lipid loading augments hypoxic paracrine signaling and promotes glioma angiogenesis and macrophage infiltration. Journal of Experimental & Clinical Cancer Research. 2019; 38: 241, 1-14. * [12.7; 25]. Corresponding author. 

Our findings high-light the role of lipid metabolism in the stressed GBM tumor niche. The identification of new drugs or repurposing of drugs from the cardiovascular field targeted at lipid metabolism for the treatment of GBM tumors is a major aim of future research.

8. Indira Chandran V, Welinder C, Månsson AS, Offer S, Freyhult E, Pernemalm M, Lund SM, Pedersen S, Lehtiö J, Marko-Varga G, Johansson MC, Englund EM, Sundgren PC, Belting M. Ultrasensitive immunoprofiling of plasma extracellular vesicles identifies syndecan-1 as a potential tool for minimally invasive diagnosis of glioma. Clinical Cancer Research. 2019;25: 3115-27. * [13.8; 93]. Corresponding author. 

We provide proof-of-concept for extracellular vesicle (EV) profiling as a strategy for non-invasive, liquid biopsy of GBM.

9. Governa V, Gonçalves de Oliveira K, Bång-Rudenstam A, Offer S, Cerezo-Magaña M, Li J, Beyer S, Johansson MC, Månsson A-S, Edvardsson C, Durmo F, Boukredine A, Jeannot P, Schmidt K, Gezelius E, Menard JA, Garza R, Jakobsson J, de Neergaard T, Sundgren PC, Tiihonen AM, Haapasalo H, Rautajoki KJ, Nordenfelt P, Darabi A, Forsberg-Nilsson K, Pietras A, Talbot H,  Bengzon J, and Belting M. “Lipid droplet-loaded macrophages as a targetable pro-tumorigenic immune cell entity in human glioblastoma”. Science Translational Medicine, accepted, 2024 *[15.8; N/A]. Corresponding author.

We introduce lipid droplet (LD)-loaded macrophages, named tumor associated foam (TAF) cells, as a previously uncharacterized immune cell entity in human GBM. We provide evidence that TAFs exhibit distinct pro-tumorigenic characteristics, correlate with worse patient outcome, and offer a potentially targetable addition to the GBM immune cell community.

 III.               Translation of research findings into a phase-III trial

Based on our findings on the role of coagulation (Belting, et al. Nature Medicine, 2004), and heparan sulfate (Belting, et al., PNAS, 2002) in tumor development, together with supportive findings by others, we conducted a clinical trial investigating the survival effect of LMWH in cancer.

10. Ek L,Gezelius E, Bergman B, Bendahl PO, Anderson H, Sundberg J, Wallberg M, Falkmer U, Verma S, Belting M. Randomized Phase III Trial of Low Molecular Weight Heparin Enoxaparin in Addition to Standard Treatment in Small Cell Lung Cancer: the RASTEN Trial. Annals of Oncology. 2018; 29: 398-404.* [51.8; 63]. Corresponding author.

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