* E-Cadherin and EpCAM expression by NSCLC tumour cells associate with normal fibroblast activation through a pathway initiated by integrin αvβ6 and maintained through TGFβ signalling.
- Fibroblasts in the tumour stroma (cancer-associated fibroblasts) influence tumour progression and response to therapeutics; little is known about the mechanisms through which the tumour cell co-opts a normal fibroblast. To study the activation of fibroblasts by tumour cells, a panel of non-small cell lung cancer (NSCLC) cell lines and normal human dermal fibroblasts were co-cultured. A subset of the NSCLC cells induced an activated cancer-associated fibroblast-like fibroblast phenotype defined by induction of fibroblast α-smooth muscle actin expression. Tumour cells that activated fibroblasts were associated with E-Cadherin and EpCAM expression and expression of integrin αvβ6. Co-culture of activating tumour cells with fibroblasts resulted in induction of transcripts associated with tumour cell invasion and growth, TGFβ1 and TGFBR1, SERPINE-1, BMP6, SPHK1 and MMP9. Fibroblast activation was inhibited by an αvβ6/8 integrin blocking antibody (264RAD) and a small molecule inhibitor of the TGF-beta type I receptor activin-like kinase (ALK5) (SB431542), demonstrating that transactivation of the TGFβ pathway initiates fibroblast activation. Both integrin and ALK5 antagonists inhibited initiation. Only ALK5 was effective when added after 3 days of co-culture. This suggests that although activation is αvβ6-dependent, once fibroblasts are activated alternative TGFβ pathway regulators maintain an activation loop. In co-culture activating cells had reduced sensitivity to selumetinib, AZD8931 and afatinib compared with mono-culture. In contrast, non-activating cells were insensitive to selumetinib and AZD8931 in both mono-culture and co-culture. In conclusion NSCLC cell lines, positive for E-Cadherin, EpCAM and αvβ6 expression, activate normal fibroblasts through avβ6/TGFβ signalling in vitro, and influence both gene expression and response to therapeutic agents.
=>表現すること, 式, 表現, 表示, 言い回し, 表現法, 表情
Overview of noun expression
The noun expression has 9 senses (first 6 from tagged texts)
1. (23) expression, look, aspect, facial expression, face -- (the feelings expressed on a person's
face; "a sad expression"; "a look of triumph"; "an angry face")
2. (18) expression, manifestation, reflection, reflexion -- (expression without words; "tears are an
expression of grief"; "the pulse is a reflection of the heart's condition")
3. (15) expression, verbal expression, verbalism -- (the communication (in speech or writing) of
your beliefs or opinions; "expressions of good will"; "he helped me find verbal expression for my
ideas"; "the idea was immediate but the verbalism took hours")
4. (5) saying, expression, locution -- (a word or phrase that particular people use in particular
situations; "pardon the expression")
5. (4) formulation, expression -- (the style of expressing yourself; "he suggested a better
formulation"; "his manner of expression showed how much he cared")
6. (4) formula, expression -- (a group of symbols that make a mathematical statement)
7. expression -- ((genetics) the process of expressing a gene)
8. construction, grammatical construction, expression -- (a group of words that form a constituent
of a sentence and are considered as a single unit; "I concluded from his awkward constructions that
he was a foreigner")
9. expression -- (the act of forcing something out by squeezing or pressing; "the expression of milk
from her breast")
--- WordNet end ---