Seeding and propagation of untransformes mouse mammary cells in the lung (Science, 2008, 321:1841-1844)

報告日期: 2009/04/10
報告時間: 17:10/18:00
報告學生: 陳家揚(英文報告)
講評老師: 鄭宏祺

Seeding and Propagation of Untransformed Mouse Mammary Cells in the Lung

Podsypanina K, Du YC, Jechlinger M, Beverly LJ, Hambardzumyan D, Varmus H.

Science, 321:1841-1844, 2008


Speaker: 陳家揚

Commentator: 鄭宏祺博士

Time/Date: 17:10-18:00, April 10, 2009

Room: 602



Cancer is the leading cause of deaths in all kinds of diseases. Metastasis of cancer is the major event that responsible for the mortality of patients. Multiple processes of cancer metastasis were broadly accepted that the metastasized cancer cells raised from the accumulation of genetic changes to acquire invasiveness abilities. Disseminated of the cancer cells to distant sites through systematic circulation and grown as secondary tumors at the late stage during cancer progression. But it is still questioned the metastatic recurrence of cancers patients after surgical removal of primary tumors and the inefficiency of the antimetastasis drugs such as metalloproteinase inhibitors. In order to realize the early dissemination ability in normal mammary cells, three animal model were used for elucidation (TOM;TOR;MTB, TOMT:IRES:Luc;MTB, and Pβ-actin-GFP transgenic mice). In these results, authors found that the untransformed normal mouse mammary cells can survive in blood stream and residence to ectopic site such as lung for a long time without tumor formation. Upon doxycyclin activated oncogene expression through mammary-specific promoter MMTV drived rtTA transcription factor, the normal mammary cells resident in lung could form tumor foci within two weeks start from doxycyclin induction. In addition, the resident mammary cells in lung can reform mammary gland in orthotropic site of recipients postpartum, suggested at least some the resident mammary cells in lung are multipoint and able to support full mammary development. This paper found that the metastatic disease can arise from untransformed mammary cells in the circulation and become dormancy at ectopic site, preparing for the relapse of the cancer. And it provide us a concept that cancer metastasis may not only occurs at late stage of cancer progression, and the transformation of the cancer may not necessary for any subsequent step of cancer metastasis.



1.  Yves Husemann et al., Systemic Spread is an Early Step in Breast Cancer. Cell, 13:58-68, 2008.

2.  K. Podsypanina et al., Oncogene Cooperation in Tumor Maintenance and Tumor Recurrence in Mouse Mammary Tumors Induced by Myc and mutant Kras. PNAS, 105:5242-5247, 2008.