(ALPHA)2(BETA)1 Integrin-Induced Breast Cancer Differentiation.

The mechanisms and receptors involved in phagocytosis by nonhematopoietic cells are not well understood. The involvement of the alpha 3 beta 1 integrin in phagocytosis of the extracellular matrix by human breast cancer cells was studied. The possible role of this integrin was suggested since alpha 3 and beta 1 but not alpha 2 subunits are concentrated at membrane sites where local degradation of fluorescently labeled gelatin occurs. Strikingly, anti-alpha 3 integrin monoclonal antibodies (mAbs) stimulate the phagocytosis of fluorescently labeled gelatin films, gelatin beads, and Matrigel films in a quantitative phagocytosis assay. Stimulation of the gelatin uptake by the anti-alpha 3 mAb is dose responsive, saturable, and time dependent. Antibodies against other integrin subunits have a lower stimulatory effect (anti-beta 1) or no significant effect (anti-alpha 2, -alpha 5, -alpha 6, and -alpha v) on gelatin phagocytosis. The synthetic HGD-6 human laminin peptide that binds specifically the alpha 3 beta 1 integrin, but not the scrambled HSGD-6 control peptide, also markedly stimulates gelatin uptake in a dose-responsive way. Furthermore, the stimulatory effects of the HGD-6 peptide and the anti-alpha 3 mAb are additive, suggesting that they might promote phagocytosis in different ways. Other laminin (YIGSR, IKVAV) and fibronectin (GRGDS) peptides have no effect on gelatin phagocytosis. Immunofluorescence shows that the alpha 3 and the beta 1, but not the alpha 2 integrin subunit, concentrate into patches on the cell surface after treatment with their respective mAbs. And, both gelatin and the alpha 3 beta 1 but not the alpha 2 beta 1 integrin are cointernalized and routed to acidic vesicles such as lysosomes. In conclusion, we demonstrate that human breast cancer cells locally degrade and phagocytose the extracellular matrix and show for the first time that the alpha 3 beta 1 integrin participates in this phagocytosis. We hypothesize that the anti-alpha 3 antibodies and the laminin peptide HGD-6 activate the alpha 3 beta 1 integrin, which results in a downstream signaling cascade stimulating phagocytosis.

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Abstract SY35-03: eIF4E in breast cancer is a master regulator of tumor cell invasion through increased translation of beta-1 integrin mRNA and TGF-beta activation

10.1158/1538-7445.am10-sy35-03 ◽

2010 ◽

Author(s):

Celine Mestel ◽

Mary-Helen Barcelos-Hoff ◽

Jiri Zavadil ◽

Silvia C. Formenti ◽

Robert J. Schneider

Keyword(s):

Breast Cancer ◽

Tumor Cell ◽

Cell Invasion ◽

Tumor Cell Invasion ◽

Tgf Beta ◽

Master Regulator ◽

Beta 1 Integrin

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Virus-Like Particles in a Human Breast Cancer: Structural Similarity to Previously Reported Particles

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100072332 ◽

1973 ◽

Vol 31 ◽

pp. 378-379

Author(s):

G. Kasnic ◽

S. E. Stewart ◽

C. Urbanski

Keyword(s):

Breast Cancer ◽

Biological Activity ◽

Human Breast Cancer ◽

Osteogenic Sarcoma ◽

Human Tumor ◽

Structural Similarity ◽

Cell Tumor ◽

Human Breast ◽

Human Tumor Cell ◽

Type Particle

We have reported the maturation of an intracisternal A-type particle in murine plasma cell tumor cultures and three human tumor cell cultures (rhabdomyosarcoma, lung adenocarcinoma, and osteogenic sarcoma) after IUDR-DMSO activation. In all of these studies the A-type particle seems to develop into a form with an electron dense nucleoid, presumably mature, which is also intracisternal. A similar intracisternal A-type particle has been described in leukemic guinea pigs. Although no biological activity has yet been demonstrated for these particles, on morphologic grounds, and by the manner in which they develop within the cell, they may represent members of the same family of viruses.

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Expression of laminin and beta-1 integrin in embryonic, neonatal, and adult rat heart

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100085216 ◽

1991 ◽

Vol 49 ◽

pp. 182-183

Author(s):

R.L. Price ◽

T.K. Borg ◽

L. Terracio ◽

M. Nakagawa

Keyword(s):

Temporal Expression ◽

Qualitative And Quantitative ◽

Adult Rat ◽

Cytoplasmic Face ◽

Extracellular Matrix Components ◽

Basement Membrane Component ◽

Beta 1 Integrin ◽

Quantitative Changes ◽

Cytoskeletal Elements ◽

External Face

Little is known about the temporal expression of extracellular matrix components (ECM) and its receptors during development of the heart. Recent reports have shown that ECM components undergo both qualitative and quantitative changes during development, and it is believed that ECM components are important in the regulation of cell migration and cell:cell and cell:ECM recognition and adhesion.Integrins are transmembrane glycoproteins which bind several ECM components on their external face and cytoskeletal elements on the cytoplasmic face. Laminin is a basement membrane component which has been recognized as an important site for cell adhesion. Both the integrins and laminin are expressed early in development and continue to be expressed in the adult heart. With their documented roles in cell recognition, and cell:cell and cell:ECM migration and adhesion these proteins appear to be important components in development of the heart, and their temporal expression may play a pivotal role in morphogenesis and myofibrillogenesis of the heart.

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Further Ultrastructural Observations on Metastatic Nodules of Human Breast Cancer

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010010086x ◽

1968 ◽

Vol 26 ◽

pp. 224-225

Author(s):

John L. Swedo ◽

R. W. Talley ◽

John H. L. Watson

Keyword(s):

Breast Cancer ◽

Human Breast Cancer ◽

Estrogen Therapy ◽

Specimen Preparation ◽

Human Breast ◽

Autophagic Vacuoles ◽

Previous Communication ◽

Linear Profiles ◽

Metastatic Nodule

Since the report, which described the ultrastructure of a metastatic nodule of human breast cancer after estrogen therapy, additional ultrastructural observations, including some which are correlative with pertinent findings in the literature concerning mycoplasmas, have been recorded concerning the same subject. Specimen preparation was identical to that in.The mitochondria possessed few cristae, and were deteriorated and vacuolated. They often contained particulates and fibrous structures, sometimes arranged in spindle-shaped bundles, Fig. 1. Another apparent aberration was the occurrence, Fig. 2 (arrows) of linear profiles of what seems to be SER, which lie between layers of RER, and are often recognizably continuous with them.It was noted that the structure of the round bodies, interpreted as within autophagic vacuoles in the previous communication, and of vesicular bodies, described morphologically closely resembled those of some mycoplasmas. Specifically, they simulated or reflected the various stages of replication reported for mycoplasmas grown on solid nutrient. Based on this observation, they are referred to here as “mycoplasma-like” structures, in anticipation of confirmatory evidence from investigations now in progress.

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