title: Leukocyte-mediated cell dissemination and metastasis: findings from multiple types of human tumors.
abstract: 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.
authors.affiliation: Armed Forces Institute of Pathology and American Registry of Pathology, Washington, District of Columbia 20306, USA. man@afip.osd.mil
authors.forename: Yan-gao
authors.initials: YG
authors.lastname: Man
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Mason
authors.forename: Russell
authors.initials: R
authors.lastname: Harley
authors.forename: Yeon Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Kangmin
authors.initials: K
authors.lastname: Zhu
authors.forename: William A
authors.initials: WA
authors.lastname: Gardner
mesh_terms: D018952:Antigens, CD34 / Q000032:analysis; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D024141:Collagen Type IV / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis; D019394:Ki-67 Antigen / Q000032:analysis; D007962:Leukocytes / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D018952:Antigens, CD34; D024141:Collagen Type IV; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D007633:Keratins