Loss of miR-200c expression induces an aggressive, invasive, and chemoresistant phenotype in non-small cell lung cancer / Paolo Ceppi, Giridhar Mudduluru, Regalla Kumarswamy, Ida Rapa, Giorgio V. Scagliotti, Mauro Papotti, and Heike Allgayer
The development of metastases is the main reason for cancer-related death in non-small cell lung cancer (NSCLC). The initiation of metastasis involves an increase in cell motility mediated by the loss of cell-cell adhesion caused by E-cadherin repression, in a process commonly known as epithelial-to-mesenchymal transition. A role for microRNA-200 family members in regulating epithelial-to-mesenchymal transition has recently been indicated but data about their expression in lung tumors is still unavailable. The present study investigated the expression of miR-200c in a panel of NSCLC cell lines (n = 9), and a strong inverse correlation with invasion was detected. Reintroduction of miR-200c into highly invasive/aggressive NSCLC cells induced a loss of the mesenchymal phenotype by restoring E-cadherin and reducing N-cadherin expression, and inhibited in vitro cell invasion as well as in vivo metastasis formation. Moreover, miR-200c overexpression restored the sensitivity of NCI-H1299 cells to cisplatin and cetuximab. Hypermethylation of the promoter region was found to be responsible for the loss of miR-200c in invasive cells, as evaluated by 5-aza-2'-deoxycytidine treatment, methylation-specific PCR, and bisulfite sequencing. In primary tumor specimens obtained from 69 patients with consecutively resected NSCLC, lower miR-200c expression levels were found to be associated with a poor grade of differentiation (P = 0.04), a higher propensity to lymph node metastases (P < 0.01), and with a lower E-cadherin expression (P = 0.01). These data indicate that the loss of miR-200c expression induces an aggressive, invasive, and chemoresistant phenotype, and that assessment of its expression could contribute to a better clinicopathologic definition of patients with NSCLC..
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
8 September 2010 2010 |
---|---|
Erschienen: |
8 September 2010 |
Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
---|---|
Enthalten in: |
Molecular cancer research - 8(2010), 9, Seite 1207-1216 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Ceppi, Paolo [VerfasserIn] |
---|
Links: |
Volltext [lizenzpflichtig] |
---|
Anmerkungen: |
Gesehen am 30.01.2023 |
---|
Umfang: |
10 |
---|
doi: |
10.1158/1541-7786.MCR-10-0052 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
1832682315 |
---|
LEADER | 01000caa a2200265 4500 | ||
---|---|---|---|
001 | 1832682315 | ||
003 | DE-627 | ||
005 | 20230710161334.0 | ||
007 | cr uuu---uuuuu | ||
008 | 230130s2010 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1158/1541-7786.MCR-10-0052 |2 doi | |
035 | |a (DE-627)1832682315 | ||
035 | |a (DE-599)KXP1832682315 | ||
035 | |a (OCoLC)1389822095 | ||
040 | |a DE-627 |b ger |c DE-627 |e rda | ||
041 | |a eng | ||
100 | 1 | |a Ceppi, Paolo |e verfasserin |0 (DE-588)1279546956 |0 (DE-627)1832684814 |4 aut | |
245 | 1 | 0 | |a Loss of miR-200c expression induces an aggressive, invasive, and chemoresistant phenotype in non-small cell lung cancer |c Paolo Ceppi, Giridhar Mudduluru, Regalla Kumarswamy, Ida Rapa, Giorgio V. Scagliotti, Mauro Papotti, and Heike Allgayer |
264 | 1 | |c 8 September 2010 | |
300 | |a 10 | ||
336 | |a Text |b txt |2 rdacontent | ||
337 | |a Computermedien |b c |2 rdamedia | ||
338 | |a Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Gesehen am 30.01.2023 | ||
520 | |a The development of metastases is the main reason for cancer-related death in non-small cell lung cancer (NSCLC). The initiation of metastasis involves an increase in cell motility mediated by the loss of cell-cell adhesion caused by E-cadherin repression, in a process commonly known as epithelial-to-mesenchymal transition. A role for microRNA-200 family members in regulating epithelial-to-mesenchymal transition has recently been indicated but data about their expression in lung tumors is still unavailable. The present study investigated the expression of miR-200c in a panel of NSCLC cell lines (n = 9), and a strong inverse correlation with invasion was detected. Reintroduction of miR-200c into highly invasive/aggressive NSCLC cells induced a loss of the mesenchymal phenotype by restoring E-cadherin and reducing N-cadherin expression, and inhibited in vitro cell invasion as well as in vivo metastasis formation. Moreover, miR-200c overexpression restored the sensitivity of NCI-H1299 cells to cisplatin and cetuximab. Hypermethylation of the promoter region was found to be responsible for the loss of miR-200c in invasive cells, as evaluated by 5-aza-2'-deoxycytidine treatment, methylation-specific PCR, and bisulfite sequencing. In primary tumor specimens obtained from 69 patients with consecutively resected NSCLC, lower miR-200c expression levels were found to be associated with a poor grade of differentiation (P = 0.04), a higher propensity to lymph node metastases (P < 0.01), and with a lower E-cadherin expression (P = 0.01). These data indicate that the loss of miR-200c expression induces an aggressive, invasive, and chemoresistant phenotype, and that assessment of its expression could contribute to a better clinicopathologic definition of patients with NSCLC. | ||
650 | 4 | |a Animals | |
650 | 4 | |a Antibodies, Monoclonal | |
650 | 4 | |a Antibodies, Monoclonal, Humanized | |
650 | 4 | |a Cadherins | |
650 | 4 | |a Carcinoma, Non-Small-Cell Lung | |
650 | 4 | |a Cell Line, Tumor | |
650 | 4 | |a Cetuximab | |
650 | 4 | |a Chick Embryo | |
650 | 4 | |a Cisplatin | |
650 | 4 | |a DNA Methylation | |
650 | 4 | |a Drug Resistance, Neoplasm | |
650 | 4 | |a Female | |
650 | 4 | |a Gene Expression Regulation, Neoplastic | |
650 | 4 | |a Humans | |
650 | 4 | |a Lung Neoplasms | |
650 | 4 | |a Lymph Nodes | |
650 | 4 | |a Male | |
650 | 4 | |a Mesoderm | |
650 | 4 | |a MicroRNAs | |
650 | 4 | |a Middle Aged | |
650 | 4 | |a Neoplasm Invasiveness | |
650 | 4 | |a Neoplasm Metastasis | |
650 | 4 | |a Phenotype | |
650 | 4 | |a Promoter Regions, Genetic | |
700 | 1 | |a Mudduluru, Giridhar |e verfasserin |4 aut | |
700 | 1 | |a Kumarswamy, Regalla |e verfasserin |4 aut | |
700 | 1 | |a Rapa, Ida |e verfasserin |4 aut | |
700 | 1 | |a Scagliotti, Giorgio V. |e verfasserin |4 aut | |
700 | 1 | |a Papotti, Mauro |e verfasserin |4 aut | |
700 | 1 | |a Allgayer, Heike |d 1969- |e verfasserin |0 (DE-588)1024987884 |0 (DE-627)720854466 |0 (DE-576)369805003 |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Molecular cancer research |d Philadelphia, Pa. : AACR, 2002 |g 8(2010), 9, Seite 1207-1216 |h Online-Ressource |w (DE-627)359783538 |w (DE-600)2097884-4 |w (DE-576)105430749 |x 1557-3125 |7 nnns |
773 | 1 | 8 | |g volume:8 |g year:2010 |g number:9 |g pages:1207-1216 |g extent:10 |
856 | 4 | 0 | |u https://doi.org/10.1158/1541-7786.MCR-10-0052 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
912 | |a GBV_USEFLAG_U | ||
912 | |a GBV_ILN_2013 | ||
912 | |a ISIL_DE-16-250 | ||
912 | |a SYSFLAG_1 | ||
912 | |a GBV_KXP | ||
912 | |a SSG-OLC-PHA | ||
912 | |a GBV_ILN_20 | ||
912 | |a GBV_ILN_22 | ||
912 | |a GBV_ILN_23 | ||
912 | |a GBV_ILN_24 | ||
912 | |a GBV_ILN_31 | ||
912 | |a GBV_ILN_39 | ||
912 | |a GBV_ILN_40 | ||
912 | |a GBV_ILN_60 | ||
912 | |a GBV_ILN_62 | ||
912 | |a GBV_ILN_63 | ||
912 | |a GBV_ILN_65 | ||
912 | |a GBV_ILN_69 | ||
912 | |a GBV_ILN_70 | ||
912 | |a GBV_ILN_73 | ||
912 | |a GBV_ILN_74 | ||
912 | |a GBV_ILN_95 | ||
912 | |a GBV_ILN_100 | ||
912 | |a GBV_ILN_101 | ||
912 | |a GBV_ILN_105 | ||
912 | |a GBV_ILN_110 | ||
912 | |a GBV_ILN_151 | ||
912 | |a GBV_ILN_161 | ||
912 | |a GBV_ILN_170 | ||
912 | |a GBV_ILN_206 | ||
912 | |a GBV_ILN_213 | ||
912 | |a GBV_ILN_230 | ||
912 | |a GBV_ILN_285 | ||
912 | |a GBV_ILN_293 | ||
912 | |a GBV_ILN_602 | ||
912 | |a GBV_ILN_2001 | ||
912 | |a GBV_ILN_2005 | ||
912 | |a GBV_ILN_2007 | ||
912 | |a GBV_ILN_2011 | ||
912 | |a GBV_ILN_2014 | ||
912 | |a GBV_ILN_2446 | ||
912 | |a GBV_ILN_4012 | ||
912 | |a GBV_ILN_4037 | ||
912 | |a GBV_ILN_4112 | ||
912 | |a GBV_ILN_4125 | ||
912 | |a GBV_ILN_4126 | ||
912 | |a GBV_ILN_4249 | ||
912 | |a GBV_ILN_4305 | ||
912 | |a GBV_ILN_4306 | ||
912 | |a GBV_ILN_4307 | ||
912 | |a GBV_ILN_4313 | ||
912 | |a GBV_ILN_4322 | ||
912 | |a GBV_ILN_4323 | ||
912 | |a GBV_ILN_4324 | ||
912 | |a GBV_ILN_4325 | ||
912 | |a GBV_ILN_4338 | ||
912 | |a GBV_ILN_4367 | ||
912 | |a GBV_ILN_4700 | ||
951 | |a AR | ||
952 | |d 8 |j 2010 |e 9 |h 1207-1216 |g 10 | ||
980 | |2 2013 |1 01 |x DE-16-250 |b 4255060517 |c 00 |f --%%-- |d --%%-- |e --%%-- |j --%%-- |y l01 |z 30-01-23 | ||
982 | |2 2013 |1 01 |x DE-16-250 |8 00 |s s |a hd2010 | ||
982 | |2 2013 |1 01 |x DE-16-250 |8 01 |s s |0 (DE-627)1410508463 |a wissenschaftlicher Artikel (Zeitschrift) | ||
982 | |2 2013 |1 01 |x DE-16-250 |8 02 |s s |a per_7 | ||
982 | |2 2013 |1 01 |x DE-16-250 |8 03 |s s |a s_10 | ||
982 | |2 2013 |1 01 |x DE-16-250 |8 04 |s p |0 (DE-627)1439807183 |a Allgayer, Heike | ||
982 | |2 2013 |1 01 |x DE-16-250 |8 04 |s k |0 (DE-627)1416467505 |a Chirurgische Klinik | ||
982 | |2 2013 |1 01 |x DE-16-250 |8 04 |s s |0 (DE-627)1410501914 |a Verfasser | ||
982 | |2 2013 |1 01 |x DE-16-250 |8 04 |s s |a pos_7 |