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2018 ; 18
(1
): 717
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Bulk tumour cell migration in lung carcinomas might be more common than
epithelial-mesenchymal transition and be differently regulated
#MMPMID29976164
Zacharias M
; Brcic L
; Eidenhammer S
; Popper H
BMC Cancer
2018[Jul]; 18
(1
): 717
PMID29976164
show ga
BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is one mechanism of
carcinoma migration, while complex tumour migration or bulk migration is another
- best demontrated by tumour cells invading blood vessels. METHODS: Thirty cases
of non-small cell lung carcinomas were used for identifying genes responsible for
bulk cell migration, 232 squamous cell and adenocarcinomas to identify bulk
migration rates. Genes expressed differently in the primary tumour and in the
invasion front were regarded as relevant in migration and further validated in
528 NSCLC cases represented on tissue microarrays (TMAs) and metastasis TMAs.
RESULTS: Markers relevant for bulk cancer cell migration were regulated
differently when compared with EMT: Twist expressed in primary tumour, invasion
front, and metastasis was not associated with TGF?1 and canonical Wnt, as Slug,
Snail, and Smads were negative and ?-Catenin expressed membraneously. In the
majority of tumours, E-Cadherin was downregulated at the invasive front, but not
absent, but, coexpressed with N-Cadherin. Vimentin was coexpressed with
cytokeratins at the invasion site in few cases, whereas fascin expression was
seen in a majority. Expression of ERK1/2 was downregulated, PLC? was only
expressed at the invasive front and in metastasis. Brk and Mad, genes identified
in Drosophila border cell migration, might be important for bulk migration and
metastasis, together with invadipodia proteins Tks5 and Rab40B, which were only
upregulated at the invasive front and in metastasis. CXCR1 was expressed equally
in all carcinomas, as opposed to CXCR2 and 4, which were only expressed in few
tumours. CONCLUSION: Bulk cancer cell migration seems predominant in AC and SCC.
Twist, vimentin, fascin, Mad, Brk, Tsk5, Rab40B, ERK1/2 and PLC? are associated
with bulk cancer cell migration. This type of migration requires an orchestrated
activation of proteins to keep the cells bound to each other and to coordinate
movement. This hypothesis needs to be proven experimentally.