bims-stacyt Biomed News
on Metabolism and the paracrine crosstalk between cancer and the organism
Issue of 2025–02–16
two papers selected by
Cristina Muñoz Pinedo, L’Institut d’Investigació Biomèdica de Bellvitge
  1. Pathways and outputs orchestrated in tumor microenvironment cells by hypoxia-induced tumor-derived exosomes in pan-cancer.
  2. A tumor-secreted protein utilizes glucagon release to cause host wasting.
  1. Cell Oncol (Dordr). 2025 Feb 10.
    Pathways and outputs orchestrated in tumor microenvironment cells by hypoxia-induced tumor-derived exosomes in pan-cancer.
    Ozel Capik, Omer Faruk Karatas.
      Hypoxia is a critical microenvironmental condition that plays a major role in driving tumorigenesis and cancer progression. Increasing evidence has revealed novel functions of hypoxia in intercellular communication. The hypoxia induced tumor derived exosomes (hiTDExs) released in high quantities by tumor cells under hypoxia are packed with unique cargoes that are essential for cancer cells' interactions within their microenvironment. These hiTDExs facilitate not only immune evasion but also promote cancer cell growth, survival, angiogenesis, EMT, resistance to therapy, and the metastatic spread of the disease. Nevertheless, direct interventions targeting hypoxia signaling in cancer therapy face challenges related to tumor progression and resistance, limiting their clinical effectiveness. Therefore, deepening our understanding of the molecular processes through which hiTDExs remodels tumors and their microenvironment, as well as how tumor cells adjust to hypoxic conditions, remains essential. This knowledge will pave the way for novel approaches in treating hypoxic tumors. In this review, we discuss recent work revealing the hiTDExs mediated interactions between tumor and its microenvironment. We have described key hiTDExs cargos (lncRNA, circRNAs, cytokines, etc.) and their targets in the receipt cells, responsible for various biological effects. Moreover, we emphasized the importance of hiTDExs as versatile elements of cell communication in the tumor microenvironment. Finally, we highlighted the effects of hiTDExs on the molecular changes in target cells by executing molecular cargo transfer between cells and altering signaling pathways. Currently, hiTDExs show promise in the treatment of diseases. Understanding the molecular processes through which hiTDExs influence tumor behavior and their microenvironment, along with how tumor cells adapt to and survive in low-oxygen conditions, remains a central focus in cancer research, paving the way for innovative strategies in treating hypoxic tumors and enhancing immunotherapy.
    Keywords:  Cancer; Exosomes; Hypoxia; Intercellular communication; Tumor microenvironment
    DOI:  https://doi.org/10.1007/s13402-025-01042-z
  2. Cell Discov. 2025 Feb 10. 11(1): 11
    A tumor-secreted protein utilizes glucagon release to cause host wasting.
    Guangming Ding, Yingge Li, Chen Cheng, Kai Tan, Yifei Deng, Huiwen Pang, Zhongyuan Wang, Peixuan Dang, Xing Wu, Elisabeth Rushworth, Yufeng Yuan, Zhiyong Yang, Wei Song.
      Tumor‒host interaction plays a critical role in malignant tumor-induced organ wasting across multiple species. Despite known regulation of regional wasting of individual peripheral organs by tumors, whether and how tumors utilize critical host catabolic hormone(s) to simultaneously induce systemic host wasting, is largely unknown. Using the conserved yki3SA-tumor model in Drosophila, we discovered that tumors increase the production of adipokinetic hormone (Akh), a glucagon-like catabolic hormone, to cause systemic host wasting, including muscle dysfunction, lipid loss, hyperglycemia, and ovary atrophy. We next integrated RNAi screening and Gal4-LexA dual expression system to show that yki3SA-gut tumors secrete Pvf1 to remotely activate its receptor Pvr in Akh-producing cells (APCs), ultimately promoting Akh production. The underlying molecular mechanisms involved the Pvf1-Pvr axis that triggers Mmp2-dependent ECM remodeling of APCs and enhances innervation from the excitatory cholinergic neurons. Interestingly, we also confirmed the similar mechanisms governing tumor-induced glucagon release and organ wasting in mammals. Blockade of either glucagon or PDGFR (homolog of Pvr) action efficiently ameliorated organ wasting in the presence of malignant tumors. Therefore, our results demonstrate that tumors remotely promote neural-associated Akh/glucagon production via Pvf1-Pvr axis to cause systemic host wasting.
    DOI:  https://doi.org/10.1038/s41421-024-00762-0
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