Whitehead Institute for Biomedical Research

Massachusetts Institute of Technology

The Brigham and Women's Hospital, Inc.

Bayer Corporation

Oncogene Science, Inc.

Whitehead Institute

Whiteland Institute for Biomedical Research

Robert Allan Weinberg

Harvey F Lodish

Xiao-Fan Wang

Herbert Y Lin

Clifford J Tabin

Scott M Bradley

Tan A Ince

Walter P Carney

Wai Leong Tam

Sara J McKenzie

Sendurai Mani

Cornelia I Bargmann

Jing Yang

Gail P Mazzara

Scott K Dessain

Sendurai A Mani

Jonathan H Morgan

Christina H Scheel

Brian Bierie

Paula Jean Marks

David F Stern

Diwakar Pattabiraman

Mai-Jing Liao

Debra Ann Petit

Scott A Valastyan

The invention provides tissue culture system for primary cells (e.g. normal mammalian primary epithelial progenitors). This system includes: a) a serum-free, chemically defined cell culture media; and, b) methods for isolation and in vitro long-term propagation of primary cells (e.g. primary epithelial cells). Primary cells so isolated and cultured can be kept undifferentiated and proliferate for many weeks (&#x3e;15 weeks) or population doubling (&#x3e;35 PD) without senescence, or any detectable genetic alterations. Upon changing media/culture conditions, these cells can be induced to differentiate. The invention also provides methods to transform normal primary cells so cultured into 'cancer stem cells.' The genetically defined cancer stem cell tumor model mimics the behavior of the disease closely, e.g., the cells are invasive, hormone responsive and metastatic when injected into mice. The tumor cells express genes that are specific to cancer stem cells identified in patient samples.

Hormone responsive tissue culture system and uses thereof

Aspects of the disclosure relate to methods that involve activating the Protein Kinase A (PKA) pathway to induce cancer stem cells (CSCs) to undergo a mesenchymal to epithelial transition. Methods provided herein are useful, in some embodiments, because they render CSCs amenable to treatment with conventional cancer therapies. In some embodiments, methods are provided that involve assaying PKA pathway activity to identify compounds that selectively target CSCs.

Methods and compositions for targeting cancer stem cells

Aspects of the invention relate to methods and related compositions for preferentially targeting cancer stem cells. In some embodiments, the methods utilize PKC-&#x3b1;/FRA1 pathway inhibitors to target carcinoma cells. Also provided are methods for identifying a candidate compound for selectively inhibiting growth of cancer stem cell, and methods for obtaining cells that have undergone an epithelial to mesenchymal transition.

Selective targeting of cancer stem cells

The invention provides compositions and methods useful for modulating epithelial-mesenchymal transition (EMT). Certain of the compositions and methods are useful for inducing epithelial cells to undergo an EMT. The invention further provides cells generated using the inventive methods and methods of use thereof. Certain of the compositions and methods are useful for inhibiting epithelial cells from undergoing an EMT. Certain of the compositions and methods are useful for inhibiting EMT in a subject in need thereof.

Compositions and methods for modulating EMT and uses thereof

Methods for preparing progenitor cells are described where epithelial cells are induced to undergo epithelial-mesenchymal transition as a result of exposure to an inducing agent or introduction of a gene therein that induces epithelial-mesenchymal transition. Progenitor cells resulting therefrom have use in cell-based therapies, among other utilities.

Progenitor cells and uses thereof

The invention relates to methods and compositions for inhibiting metastasis, such as by inhibiting FOXC2 expression or activity. The invention further relates to methods of prognosticating, diagnosing, and assisting in the diagnosis of metastasis in an individual, or of determining the metastatic potential of a tumor. The invention further relates to methods of identifying agents which inhibit metastasis.

Methods of diagnosing, preventing and treating cancer metastasis

Use of FOXC2 in diagnosing, preventing and treating cancer metastasis

The present invention provides in one aspect novel fusion partner cells that ectopically express one or more genes that alter the phenotype of a hybrid cell made from a fusion of the fusion partner cell and a fusion cell, hybrid cell lines produced using the fusion partner cells. The invention in another aspect provides antibodies produced by certain hybrid cell lines, and compositions containing one or a combination of such antibodies or antigen-binding fragments thereof. The invention also provides in another aspect methods of using the antibodies or antigen-binding fragments thereof for diagnosis and treatment of diseases characterized by the antigens specifically bound by the antibodies.

Fusion partner cells and uses thereof

This invention relates to a substantially purified p100 which is a human neu related protein having a molecular weight in the range from about 97,000 daltons to about 115,000 daltons which corresponds substantially to the extracellular domain of the human neu gene product, said protein being detectable in a biological fluid. In another embodiment this invention relates to assays for detecting this protein. Finally, this invention also concerns monoclonal antibodies which are capable of binding to p100.

Detection and quantification of neu related proteins in the biological fluids of humans

Experiments designed to define the differences between the 21 oncogene of DNA isolated from human bladder cancer cells and its corresponding proto-oncogene are described herein. Also described is the determination of the difference between the rat neu oncogene and its corresponding proto-oncogene. Also described are nucleic acid probes reactive with regions of the proto-oncogene or oncogene, as are methods for their use in detecting the occurrence of the two types of genes. Antibodies specific for gene products encoded by the neu genes are also described, as are methods for their use.

Oncogenes and methods for their detection

DNA encoding TGF-&bgr; TYPE III receptor of mammalian origin, DNA encoding TGF-&bgr; type II receptor of mammalian origin, TGF-&bgr; type III receptor, TGF-&bgr; type II receptor and uses therefor.

TGF-&bgr; type receptor cDNAs encoded products and uses therefor

DNA encoding TGF-.beta. TYPE III receptor of mammalian origin, DNA encoding TGF-.beta. type II receptor of mammalian origin, TGF-.beta. type III receptor. TGF-.beta. type II receptor and uses therefor.

Modulation of TGF-.beta. by TGF-.beta. type III receptor polypeptides

The mammalian TGF-.beta. type II receptor has been cloned. Recombinant TGF-.beta.-binding receptor polypeptides are useful to alter the binding of TGF-.beta. to its receptors and to modulate the effects of TGF-.beta. in vivo.

Growing community of inventors

Brookline, MA, United States of America

Robert Allan Weinberg