Lani
07-05-2008, 08:57 AM
Am J Pathol. 2008 Jul 3. [Epub ahead of print]
The Lymphovascular Embolus of Inflammatory Breast Cancer Expresses a Stem Cell-Like Phenotype.
Xiao Y, Ye Y, Yearsley K, Jones S, Barsky SH.
From the Department of Pathology, The Ohio State University College of Medicine, Columbus, Ohio.
Inflammatory breast carcinoma (IBC) is a particularly lethal form of breast cancer characterized by exaggerated lymphovascular invasion, which is a phenotype recapitulated in our human xenograft MARY-X. MARY-X generated spheroids in vitro that resemble the embryonal blastocyst. Because of the resemblance of the spheroids to the embryonal blastocyst and their resistance to traditional chemotherapy/radiotherapy, we hypothesized that the spheroids expressed a stem cell-like phenotype. MARY-X spheroids expressed embryonal stem cell markers including stellar, rex-1, nestin, H19, and potent transcriptional factors, oct-4, nanog, and sox-2, which are associated with stem cell self-renewal and developmental potential. Most importantly, MARY-X spheroids expressed a cancer stem cell profile characterized by CD44(+)/CD24(-/low), ALDH1, and most uniquely, CD133. A significant percentage of single cells of MARY-X exhibited distinct proliferative and morphogenic potencies in vitro. As few as 100 cells derived from single-cell clonogenic expansion were tumorigenic with recapitulation of the IBC phenotype. Prototype stem cell signaling pathways such as notch3 were active in MARY-X. The stem cell phenotype exhibited by MARY-X also was exhibited by the lymphovascular emboli of human IBC cases independent of their molecular subtype. This stem cell-like phenotype may contribute to the aggressive nature of IBC but also may lend itself to selective targeting.
PMID: 18599608 [PubMed - as supplied by publisher
Dr. Max Wicha of University of Michigan has started a new clinical trial of an
anti-cancer stem cell sheddase (targetted therapy) at four institutions, he announced at his talks at both the AACR Annual meeting (video online) and ASCO(video online as well). In each video he announced the trials and trial centers. This is the first ever trial for an agent specifically against cancer stem cells.
Looks like patients with IBC may be among those who could potentially benefit from this trial.
The Lymphovascular Embolus of Inflammatory Breast Cancer Expresses a Stem Cell-Like Phenotype.
Xiao Y, Ye Y, Yearsley K, Jones S, Barsky SH.
From the Department of Pathology, The Ohio State University College of Medicine, Columbus, Ohio.
Inflammatory breast carcinoma (IBC) is a particularly lethal form of breast cancer characterized by exaggerated lymphovascular invasion, which is a phenotype recapitulated in our human xenograft MARY-X. MARY-X generated spheroids in vitro that resemble the embryonal blastocyst. Because of the resemblance of the spheroids to the embryonal blastocyst and their resistance to traditional chemotherapy/radiotherapy, we hypothesized that the spheroids expressed a stem cell-like phenotype. MARY-X spheroids expressed embryonal stem cell markers including stellar, rex-1, nestin, H19, and potent transcriptional factors, oct-4, nanog, and sox-2, which are associated with stem cell self-renewal and developmental potential. Most importantly, MARY-X spheroids expressed a cancer stem cell profile characterized by CD44(+)/CD24(-/low), ALDH1, and most uniquely, CD133. A significant percentage of single cells of MARY-X exhibited distinct proliferative and morphogenic potencies in vitro. As few as 100 cells derived from single-cell clonogenic expansion were tumorigenic with recapitulation of the IBC phenotype. Prototype stem cell signaling pathways such as notch3 were active in MARY-X. The stem cell phenotype exhibited by MARY-X also was exhibited by the lymphovascular emboli of human IBC cases independent of their molecular subtype. This stem cell-like phenotype may contribute to the aggressive nature of IBC but also may lend itself to selective targeting.
PMID: 18599608 [PubMed - as supplied by publisher
Dr. Max Wicha of University of Michigan has started a new clinical trial of an
anti-cancer stem cell sheddase (targetted therapy) at four institutions, he announced at his talks at both the AACR Annual meeting (video online) and ASCO(video online as well). In each video he announced the trials and trial centers. This is the first ever trial for an agent specifically against cancer stem cells.
Looks like patients with IBC may be among those who could potentially benefit from this trial.