ORTHOTOPIC TUMOUR INDUCTION PROTOCOL SHAPES TUMOUR MICROENVIRONMENT

Tumour cell number at orthotopic implantation in the 4T1 TNBC mammary model strongly reshapes tumour microenvironment features, including hypoxia, necrosis, proliferation, vascular integrity, and immune infiltration.

• Why it matters: Orthotopic TNBC models vary in the number of cells used to start tumours, but how this choice affects tumour biology and downstream dissemination remains insufficiently defined.
• What they did: The study implanted 4T1 tumour cells into the mammary gland using different initiation cell numbers, then compared early growth and microenvironment readouts including HIF-1 staining, necrosis, proliferation, vascular markers, and immune cell infiltration.
• The result: High-density tumours showed increased HIF-1 staining and necrosis with altered vascular-associated markers and greater macrophage recruitment, while low-density tumours were more proliferative, less necrotic, and had higher PDGFR{beta} staining; systemic dissemination occurred within days across all conditions.

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