肿瘤自接种的相关机制与生物学意义

The traditional theory of tumor metastasis emphasizes the unidirectional spread of cancer cells from the primary site to distant organs. However, the recently proposed “tumor self-seeding” model reveals that circulating tumor cells(CTC) can re-home to the primary tumor or established metastatic lesions, forming a bidirectional or even multidirectional cellular circulation network, thereby driving tumor progression, increased heterogeneity, and therapy resistance. This article systematically elucidates the multi-stage intrinsic logic of tumor self-seeding: from the initiation and shedding of aggressive subclones, to the survival and immune evasion of CTC in circulation, followed by homing mediated by chemotactic signals, and finally the re-colonization and tumor self-reinforcement through matrix remodeling. The article further outlines the key molecular hubs regulating this process, including homing mediators such as IL-6/IL-8, pathways governing cellular plasticity and immune evasion like the N-cadherin/Rac1 axis, hyperactivation of TGF-β signaling driven by microenvironmental extracellular vesicles, and the ENPP1/HP axis promoting local recurrence. Finally, the article delves into the profound and complex interplay between self-seeding and classical metastatic pathways. They share core molecular mechanisms and constitute a multidirectional, systemic dissemination network, providing a novel theoretical framework for understanding tumor persistence and heterogeneity, and pointing the way for developing new therapeutic strategies targeting this circulatory process.