Authors
Konstantin Stoletov, Seyedeh Sara Karimian, Douglas Brown, Alice Amitrano, Bishwa Ranjan Si, Varinder Madhav Verma, Somnath Gupta, Amirali B Bukhari, Suellen Lamb, Konstantinos Konstantopoulos, Gane Ka-Shu Wong, John D Lewis
Published in
Oncogene. Oct 10, 2026. Epub Oct 10, 2026.
Abstract
Cancer cell intravasation requires both directed invasion toward the vasculature and access to functional blood vessels that act as intravasation sites. Using intravital video microscopy, we identified the peptide hormone adrenomedullin 2 (ADM2) as a critical regulator of this process. ADM2 was selectively upregulated in a highly invasive subpopulation of cancer cells that localize near blood vessels and actively drive intravasation. Knockdown of ADM2 significantly impaired intratumoral cancer cell invasion and intravasation in a chicken embryo metastasis model and in vitro. ADM2-deficient tumors exhibited reduced vascularization, limiting the availability of competent intravasation sites. Moreover, loss of ADM2 suppressed the formation of invasive metastatic lesions, indicating a requirement for ADM2 at multiple stages of the metastatic cascade. Consistently, targeting ADM2 in a mouse metastasis model inhibited the development of large intratumoral blood vessels and reduced metastasis. Collectively, these findings establish ADM2 as a previously unrecognized regulator of tumor-vascular interactions and highlight its potential as a therapeutic target to simultaneously disrupt invasion, vascular support, and metastatic dissemination.
PMID:
42859189
Bibliographic data and abstract were imported from PubMed on 11 Oct 2026.
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