Paraskevi Heldin research group

We aim to investigate the molecular mechanisms that lead to excessive hyaluronan accumulation in certain tumors and infections, resulting in the over-activity of CD44 signaling. Such knowledge is crucial for better management of metastasis and infections.

Targeting hyaluronan-CD44 signaling in cancer and infection

During tumor progression, cell surface molecules such as CD44 function as microenvironmental sensors functioning as metastasis suppressors or promoters in a cellular context. Our research focus on the growth factor-mediated induced hyaluronan-CD44 signaling during inflammation, cancer and infection. We found that increased hyaluronan synthase 2 (HAS2)-synthesized hyaluronan activated CD44 signaling during Dengue virus infection-induced inflammation, disrupting endothelial integrity. Increased serum hyaluronan levels are an early predictor of warning signs for severe dengue virus infection. In certain tumors, such as gliomas, a CD44/hyaluronan feedback circuit drives tumor progression, and is related to the expression of PDGF and PDGF receptor family members.

Group members

Research leader: Paraskevi Heldin

Group members: Arianna Parnigoni

Publications

Hyaluronan-Induced CD44-iASPP Interaction Affects Fibroblast Migration and Survival

Lin, Chun-Yu; Basu, Kaustuv; Ruusala, Aino; Kozlova, Inna et al.

Part of Cancers, 2023
- DOI for Hyaluronan-Induced CD44-iASPP Interaction Affects Fibroblast Migration and Survival
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CD44 Depletion in Glioblastoma Cells Suppresses Growth and Stemness and Induces Senescence

Kolliopoulos, Constantinos; Ali, Mohamad Moustafa; Castillejo-Lopez, Casimiro; Heldin, Carl-Henrik et al.

Part of Cancers, 2022
- DOI for CD44 Depletion in Glioblastoma Cells Suppresses Growth and Stemness and Induces Senescence
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Hyaluronan nanoscale clustering and Hyaluronan synthase 2 expression are linked to the invasion of child fibroblasts and infantile fibrosarcoma in vitro and in vivo

Tonge, Joseph J.; Notley, Scott, V; Dunning, Mark J.; Lopez-Guajardo, Ana et al.

Part of Scientific Reports, 2022
- DOI for Hyaluronan nanoscale clustering and Hyaluronan synthase 2 expression are linked to the invasion of child fibroblasts and infantile fibrosarcoma in vitro and in vivo
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Identification of a Small Molecule Inhibitor of Hyaluronan Synthesis, DDIT, Targeting Breast Cancer Cells

Karalis, Theodoros; Shiau, Andrew K. K.; Gahman, Timothy C. C.; Skandalis, Spyros S. S. et al.

Part of Cancers, 2022
- DOI for Identification of a Small Molecule Inhibitor of Hyaluronan Synthesis, DDIT, Targeting Breast Cancer Cells
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The natural antisense transcript HAS2-AS1 regulates breast cancer cells aggressiveness independently from hyaluronan metabolism

Parnigoni, Arianna; Caon, Ilaria; Teo, Wei Xuan; Hua, San Hue et al.

Part of Matrix Biology, p. 140-161, 2022
- DOI for The natural antisense transcript HAS2-AS1 regulates breast cancer cells aggressiveness independently from hyaluronan metabolism
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