Transcriptional programs induced by c-Myb prevent lung seeding
of mammary tumors

a 2014

Transcriptional programs induced by c-Myb prevent lung seeding of mammary tumors

KNOPFOVÁ, Lucia, Petr BENEŠ, Michal MASAŘÍK, Pierre JURDIC, Lubor BORSIG et. al.

Základní údaje

Originální název

Transcriptional programs induced by c-Myb prevent lung seeding of mammary tumors

Název česky

Transkripční programy indukované proteinem c-Myb brání kolonizaci plic prsními nádory

Autoři

KNOPFOVÁ, Lucia, Petr BENEŠ, Michal MASAŘÍK, Pierre JURDIC, Lubor BORSIG a Jan ŠMARDA

Vydání

Goodbye Flat Biology: 3D Models and Tumour Microenvironment, 2014

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Obor

Genetika a molekulární biologie

Stát vydavatele

Německo

Utajení

není předmětem státního či obchodního tajemství

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova česky

c-Myb, metastázy, nádorová kolonizace

Klíčová slova anglicky

c-Myb, metastasis, lung seeding

Změněno: 6. 1. 2015 13:58, Mgr. Lucia Knopfová, Ph.D.

Anotace

ORIG CZ

V originále

Metastasis is the cause of most cancer-related deaths. Overt metastasis is the end result of a multistep process that involves dissemination of tumor cells to distant organs and subsequent adaptation to foreign tissue microenvironments. Success in distant colonization is dictated by both intrinsic characteristics of tumor cells and the permissive/restrictive conditions in secondary tissue. By repeated challenge of 4T1 mammary carcinoma cells with lung microenvironment in vivo, we selected cells highly productive in short-term lung seeding. To search for molecular mechanisms responsible for seeding of tumor cells in the lungs we analyzed expression of the candidate proteins and discovered significant down-regulation of the c-Myb transcription factor in the selected cells. We documented previously that deregulation of c-Myb in mammary tumors results in altered metastasis pattern in mice: the Myb-overexpressing tumors generated liver and bone metastases, while control tumors spread spontaneously to liver, bone and lung. Here we demonstrated that Myb overexpression in 4T1 cells attenuated the lung seeding upon intravenous injection. This implies that c-Myb might be critical for early steps of metastatic colonization of the lungs. The early events occurring in the metastatic site include arrest of tumor cells in the endothelium, extravasation and survival in a hostile microenvironment. Specific features of endothelium and vascular permeabilization in lung, compared to liver and bone marrow, prompted us to test whether c-Myb affects transendothelial migration (TEM) of mammary cancer cells. The interaction of 4T1 cells with different types of endothelial cells was monitored by impedance-based cell analyzer or microscopy in transwell set-up, as well as imaged on the 3D matrix by confocal microscope. We demonstrated that c-Myb slightly reduced transmigration of 4T1 cells through endothelium. Analysis of publically available microarray data revealed that breast cancer cell lines capable of TEM (TEM+) express lower amounts of MYB mRNA than TEM- cell lines. In addition, pulmonary metastases of human breast carcinoma exhibit lower MYB expression than extra-pulmonary metastases (Oncomine). We hypothesize that c-Myb-induced transcriptional programs alter tumor-stroma interactions at the metastatic site in an organ-specific manner.

Česky

Deregulace transkripčního faktoru c-Myb v prsních nádorových buňkách zasahuje do interakce nádorových buněk s buňkami hostitele, zejména s buňkami endotelu, což způsobuje odlišnosti v metastatickém rozsevu těchto nádorů.

Návaznosti

CZ.1.07/2.3.00/20.0183, interní kód MU

Název: Centrum experimentální biomedicíny (Akronym: CEB)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Centrum experimentální biomedicíny, 2.3 Lidské zdroje ve výzkumu a vývoji

Citovat

KNOPFOVÁ, Lucia, Petr BENEŠ, Michal MASAŘÍK, Pierre JURDIC, Lubor BORSIG a Jan ŠMARDA. Transcriptional programs induced by c-Myb prevent lung seeding of mammary tumors. In Goodbye Flat Biology: 3D Models and Tumour Microenvironment. 2014.

@proceedings{1215047,
   author = {Knopfová, Lucia and Beneš, Petr and Masařík, Michal and Jurdic, Pierre and Borsig, Lubor and Šmarda, Jan},
   booktitle = {Goodbye Flat Biology: 3D Models and Tumour Microenvironment},
   keywords = {c-Myb, metastasis, lung seeding},
   language = {eng},
   title = {Transcriptional programs induced by c-Myb prevent lung seeding of mammary tumors},
   year = {2014}
}

TY  - CONF
ID  - 1215047
AU  - Knopfová, Lucia - Beneš, Petr - Masařík, Michal - Jurdic, Pierre - Borsig, Lubor - Šmarda, Jan
PY  - 2014
TI  - Transcriptional programs induced by c-Myb prevent lung seeding of mammary tumors
KW  - c-Myb, metastasis, lung seeding
N2  - Metastasis is the cause of most cancer-related deaths. Overt metastasis is the end result of a multistep process that involves dissemination of tumor cells to distant organs and subsequent adaptation to foreign tissue microenvironments. Success in distant colonization is dictated by both intrinsic characteristics of tumor cells and the permissive/restrictive conditions in secondary tissue. By repeated challenge of 4T1 mammary carcinoma cells with lung microenvironment in vivo, we selected cells highly productive in short-term lung seeding. To search for molecular mechanisms responsible for seeding of tumor cells in the lungs we analyzed expression of the candidate proteins and discovered significant down-regulation of the c-Myb transcription factor in the selected cells. We documented previously that deregulation of c-Myb in mammary tumors results in altered metastasis pattern in mice: the Myb-overexpressing tumors generated liver and bone metastases, while control tumors spread spontaneously to liver, bone and lung. Here we demonstrated that Myb overexpression in 4T1 cells attenuated the lung seeding upon intravenous injection. This implies that c-Myb might be critical for early steps of metastatic colonization of the lungs. The early events occurring in the metastatic site include arrest of tumor cells in the endothelium, extravasation and survival in a hostile microenvironment. Specific features of endothelium and vascular permeabilization in lung, compared to liver and bone marrow, prompted us to test whether c-Myb affects transendothelial migration (TEM) of mammary cancer cells. The interaction of 4T1 cells with different types of endothelial cells was monitored by impedance-based cell analyzer or microscopy in transwell set-up, as well as imaged on the 3D matrix by confocal microscope. We demonstrated that c-Myb slightly reduced transmigration of 4T1 cells through endothelium. Analysis of publically available microarray data revealed that breast cancer cell lines capable of TEM (TEM+) express lower amounts of MYB mRNA than TEM- cell lines. In addition, pulmonary metastases of human breast carcinoma exhibit lower MYB expression than extra-pulmonary metastases (Oncomine). We hypothesize that c-Myb-induced transcriptional programs alter tumor-stroma interactions at the metastatic site in an organ-specific manner.
ER  -

KNOPFOVÁ, Lucia, Petr BENEŠ, Michal MASAŘÍK, Pierre JURDIC, Lubor BORSIG a Jan ŠMARDA. Transcriptional programs induced by c-Myb prevent lung seeding of mammary tumors. In \textit{Goodbye Flat Biology: 3D Models and Tumour Microenvironment}. 2014.

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