Leukocyte-mediated cell dissemination and metastasis: Findings from multiple types of human tumors

Yan Gao Man*, Jeffrey Mason, Russell Harley, Yeon Ho Kim, Kangmin Zhu, William A. Gardner

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Our previous studies revealed that leukocyte infiltration could trigger human breast and prostate tumor invasion through focal disruptions of the tumor capsule, which selectively favors monoclonal proliferation of tumor progenitors or a biologically more aggressive cell clone overlying the focal disruptions. Our current study, involving multiple types of human tumors, further shows that leukocyte infiltration could also trigger tumor metastasis through the following pathways: [1] more leukocytes migrate to focally disrupted tumor capsules, which forms leukocyte aggregates surrounding newly formed tumor cell clusters, [2] the physical movement of leukocytes into proliferating tumor cells disrupts the intercellular junctions and cell-surface adhesion molecules, causing the disassociation of tumor cells from the tumor core, [3] leukocytes are conjoined with some of these tumor cells through plasma membrane fusion, creating tumor cell-leukocyte chimeras (TLCs), and [4] the leukocyte of TLCs impart migratory capacity to associated tumor cell partners, physically dragging them to different tissue sites. Our findings suggest a novel pathway for tumor cell dissemination from the primary sites and the subsequent journey to new sites. Our findings also provide a unique explanation for the cellular mechanism of leukocytes on tumor invasion and metastasis. If confirmed, our hypothesis and technical approach may significantly facilitate early detection and intervention of tumor invasion and metastasis.

Original languageEnglish
Pages (from-to)1154-1167
Number of pages14
JournalJournal of Cellular Biochemistry
Issue number4
StatePublished - Apr 2011
Externally publishedYes


  • Intercellular junctions
  • Leukocytes
  • Lymphocytes
  • Surface adhesion molecules
  • Tumor invasion
  • Tumor metastasis
  • Tumor stem cell


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