Systemic spread is an early step in breast cancer

Area of Science:

• Oncology
• Cancer Biology
• Metastasis Research

Background:

• Metastasis is traditionally considered a late event in cancer progression.
• The timing and origin of disseminated tumor cells remain areas of active investigation.

Purpose of the Study:

• To investigate the systemic dissemination of tumor cells from the earliest stages of epithelial alterations.
• To determine if early-disseminated cancer cells possess the potential to form distant metastases.

Main Methods:

• Utilized HER-2 and PyMT transgenic mouse models to study early tumor cell dissemination.
• Transplanted single premalignant glands into wild-type mice to assess metastatic potential.
• Analyzed disseminated tumor cells and micrometastasis in bone marrow and lungs.
• Examined karyotypic abnormalities in disseminated cancer cells from mouse models and human ductal carcinoma in situ.

Main Results:

• Systemic dissemination of tumor cells was observed from the earliest epithelial alterations in mouse models.
• Single premalignant glands led to disseminated tumor cells and micrometastasis in recipient mice.
• The number of disseminated cells and their abnormalities were comparable between small and large tumors.
• A small number of early-disseminated cancer cells (80) were sufficient to induce lethal carcinosis upon activation.

Conclusions:

• Tumor cells can disseminate systemically at the earliest stages of cancer development, contrary to established beliefs.
• Early-disseminated cancer cells possess the capacity for metastasis, potentially explaining metachronous metastasis.
• The findings highlight the critical role of early dissemination and dormancy in cancer progression and metastasis.