Anine Aunan

• Aunan, Anine; Claeyssen, Charlotte; Abdelhalim, Mohamed & Ruzzin, Jerome Nicolas Marius (2026). Transcriptomic profiling of co-cultured cancer-host cells identifies hypoxia as a driver of the skeletal muscle cell’s anti-proliferative effect on cancer cells | Oncogenesis. Oncogenesis. doi: 10.1038/s41389-026-00601-9. Fulltekst i vitenarkiv Vis sammendrag

  Cancer metastasis is the leading cause of cancer-related death. While organs such as the lung are hotspots for metastases, others -like skeletal muscle- remain rarely colonized, a phenomenon that remains poorly understood. In this study, we show that EO771 breast cancer cells proliferated robustly when co-cultured with MLg lung stromal cells, whereas their proliferation was restrained when maintained in direct contact with differentiated C2C12 skeletal muscle myotubes. Notably, these effects were not cell-type-specific, as similar results were obtained with 4T1 breast cancer cells and Sol8 myotubes. After two days of co-culture, both cancer and host cells (MLg and C2C12) exhibited distinct niche-specific transcriptional remodeling. Strikingly, the poorly proliferative EO771 cells co-cultured with C2C12 myotubes acquired a hypoxia-associated gene-expression signature despite normoxic conditions (~20% O₂), showing that muscle cells reprogram cancer cells into a hypoxic, anti-proliferative state. Under hypoxic conditions, we confirmed that the depletion of oxygen allows C2C12 cells to nearly abolish EO771 proliferation. Neither exogenous lactate, culture acidosis, their combination, altered glucose levels, nor conditioned medium could reproduce the suppressive environment created by C2C12 myotubes. In contrast, MLg cells induced minimal transcriptional changes in EO771 cells and were themselves broadly reprogrammed by the cancer cells. Moreover, hypoxia enhanced EO771 proliferation in MLg co-cultures, emphasizing the permissive nature of the MLg environment. Collectively, these findings uncover a unique, paradoxical, muscle-induced pseudo-hypoxic program that restricts cancer cell proliferation. They also highlight the need for caution in targeting hypoxia signaling in anti-metastatic therapies, as such interventions could weaken skeletal muscle’s natural defense against tumor colonization.

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• Aunan, Anine & Ruzzin, Jerome Nicolas Marius (2026). Molecular Mechanisms Preserving Skeletal Muscle Integrity and Capacity to Resist Cancer Cell Colonization. Universitetet i Oslo. ISSN 9788234808753. Fulltekst i vitenarkiv Vis sammendrag

  Preserving skeletal muscle integrity is essential for a healthy life. This thesis investigates the mechanisms underlying skeletal muscle deterioration during physiological aging and cancer-associated cachexia, while also exploring the intrinsic capacity of skeletal muscle to suppress cancer cell proliferation. Findings presented in this work demonstrate that the aryl hydrocarbon receptor (AHR) is required for skeletal muscle homeostasis. Myofiber AHR loss results in skeletal muscle decline in adult mice, while AHR activation with FICZ prevents dexamethasone induced atrophy by stimulating anabolic signaling and suppressing atrogene expression. Furthermore, myofiber AHR loss enhances breast cancer-induced muscle wasting in female mice, indicating that AHR protects skeletal muscle under catabolic stress. In addition, the thesis presents an in vitro co-culture model in which C2C12 myotubes suppress breast cancer cell proliferation and induce a pseudohypoxic transcriptional program. Hypoxia further inhibits cancer cell outgrowth on myotubes, an effect not replicated by myotube-secreted factors alone. Collectively, these findings identify AHR as a key regulator of muscle integrity and implicate hypoxia as a contributor of skeletal muscle cell’s resistance to cancer cell colonization.

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