Mohammad Shomali - Academia.edu (original) (raw)

Papers by Mohammad Shomali

Research paper thumbnail of The disintegrin domain of ADAM17 antagonises fibroblast-carcinoma cell interactions

International Journal of Oncology, 2013

The malignant phenotype of carcinoma cells depends on their ability to invade into their microenv... more The malignant phenotype of carcinoma cells depends on their ability to invade into their microenvironment promoting metastasis. Therefore, carcinoma cells overexpress many proteins, including A disintegrin and metalloproteases (ADAMs). ADAM17 is expressed by different cancer cell lines and possesses adhesive as well as enzymatic activities. To address the adhesive properties in tumour progression the recombinantly expressed soluble disintegrin domain of ADAM17 was employed. Fibroblasts and carcinoma cells adhere to the immobilized disintegrin domain. Additionally, the soluble disintegrin domain impaired fibroblast-carcinoma cell interactions and increased the shedding activity of ADAM17. Silencing of ADAM17 in fibroblasts or in carcinoma cells decreases cell-cell interaction between these cells. In summary, our results show that the adhesive properties of ADAM17 are mediated by its disintegrin domain and enables carcinoma cells to interact with their microenvironment.

Research paper thumbnail of Functional Expression of NOD2 in Freshly Isolated Human Peripheral Blood γδ T Cells

Scandinavian Journal of Immunology, 2011

Research paper thumbnail of Development of sandwich ELISA for detection and quantification of human and murine a disintegrin and metalloproteinase17

Journal of Immunological Methods, 2011

ADAM17 (a disintegrin and metalloproteinase-containing protein 17) is a membrane-bound metallopro... more ADAM17 (a disintegrin and metalloproteinase-containing protein 17) is a membrane-bound metalloproteinase, implicates in many physiological processes, including cell migration and proliferation. Of particular note, most of the studies so far are restricted on the analysis of ADAM17 mRNA levels. In this study we generated, utilizing hybridoma technology, three monoclonal antibodies (mAbs) (A 300, A 309 and A 318) against the extracellular domain of human ADAM17 to enable quantification of protein expression. The specificity of these mAbs against ADAM17 was tested by enzyme-linked immunoadsorbent assay (ELISA), flourescenceactivated cell sorting (FACS) and western blotting. In order to quantify human and murine ADAM17 expression two pairs of these mAbs (biotinylated A 309 in combination with A 300 and biotinylated A 300 in combination with A 318), were used to develop sandwich ELISA. A panel of monoclonal antibodies was generated for first time to measure mouse ADAM17 with a sensitivty of 2 ng/ml. Such systems provide a useful tool to quantify protein levels of ADAM17 and are valuable tools for diagnostic purposes.

Research paper thumbnail of ADAM17-overexpressing breast cancer cells selectively targeted by antibody–toxin conjugates

Cancer Immunology, Immunotherapy, 2012

A disintegrin and metalloproteinase 17 (ADAM17) is signiWcantly upregulated not only in malignant... more A disintegrin and metalloproteinase 17 (ADAM17) is signiWcantly upregulated not only in malignant cells but also in the pro-inXammatory microenvironment of breast cancer. There, ADAM17 is critically involved in the processing of tumor-promoting proteins. Therefore, ADAM17 appears to be an attractive therapeutic target to address not only tumor cells but also the tumorpromoting environment. In a previous study, we generated a monoclonal anti-ADAM17 antibody (A300E). Although showing no complement-dependent cytotoxicity or antibody-dependent cellular cytotoxicity, the antibody was rapidly internalized by ADAM17-expressing cells and was able to transport a conjugated toxin into target cells. As a result, doxorubicin-coupled A300E or Pseudomonas exotoxin A-loaded A300E was able to kill ADAM17-expressing cells. This eVect was strictly dependent on the presence of ADAM17 on the surface of target cells. As a proof of principle, both immunotoxins killed MDA-MB-231 breast cancer cells in an ADAM17-dependent manner. These data suggest that the use of anti-ADAM17 monoclonal antibodies as a carrier might be a promising new strategy for selective anti-cancer drug delivery.

Research paper thumbnail of The disintegrin domain of ADAM17 antagonises fibroblast-carcinoma cell interactions

International Journal of Oncology, 2013

The malignant phenotype of carcinoma cells depends on their ability to invade into their microenv... more The malignant phenotype of carcinoma cells depends on their ability to invade into their microenvironment promoting metastasis. Therefore, carcinoma cells overexpress many proteins, including A disintegrin and metalloproteases (ADAMs). ADAM17 is expressed by different cancer cell lines and possesses adhesive as well as enzymatic activities. To address the adhesive properties in tumour progression the recombinantly expressed soluble disintegrin domain of ADAM17 was employed. Fibroblasts and carcinoma cells adhere to the immobilized disintegrin domain. Additionally, the soluble disintegrin domain impaired fibroblast-carcinoma cell interactions and increased the shedding activity of ADAM17. Silencing of ADAM17 in fibroblasts or in carcinoma cells decreases cell-cell interaction between these cells. In summary, our results show that the adhesive properties of ADAM17 are mediated by its disintegrin domain and enables carcinoma cells to interact with their microenvironment.

Research paper thumbnail of Functional Expression of NOD2 in Freshly Isolated Human Peripheral Blood γδ T Cells

Scandinavian Journal of Immunology, 2011

Research paper thumbnail of Development of sandwich ELISA for detection and quantification of human and murine a disintegrin and metalloproteinase17

Journal of Immunological Methods, 2011

ADAM17 (a disintegrin and metalloproteinase-containing protein 17) is a membrane-bound metallopro... more ADAM17 (a disintegrin and metalloproteinase-containing protein 17) is a membrane-bound metalloproteinase, implicates in many physiological processes, including cell migration and proliferation. Of particular note, most of the studies so far are restricted on the analysis of ADAM17 mRNA levels. In this study we generated, utilizing hybridoma technology, three monoclonal antibodies (mAbs) (A 300, A 309 and A 318) against the extracellular domain of human ADAM17 to enable quantification of protein expression. The specificity of these mAbs against ADAM17 was tested by enzyme-linked immunoadsorbent assay (ELISA), flourescenceactivated cell sorting (FACS) and western blotting. In order to quantify human and murine ADAM17 expression two pairs of these mAbs (biotinylated A 309 in combination with A 300 and biotinylated A 300 in combination with A 318), were used to develop sandwich ELISA. A panel of monoclonal antibodies was generated for first time to measure mouse ADAM17 with a sensitivty of 2 ng/ml. Such systems provide a useful tool to quantify protein levels of ADAM17 and are valuable tools for diagnostic purposes.

Research paper thumbnail of ADAM17-overexpressing breast cancer cells selectively targeted by antibody–toxin conjugates

Cancer Immunology, Immunotherapy, 2012

A disintegrin and metalloproteinase 17 (ADAM17) is signiWcantly upregulated not only in malignant... more A disintegrin and metalloproteinase 17 (ADAM17) is signiWcantly upregulated not only in malignant cells but also in the pro-inXammatory microenvironment of breast cancer. There, ADAM17 is critically involved in the processing of tumor-promoting proteins. Therefore, ADAM17 appears to be an attractive therapeutic target to address not only tumor cells but also the tumorpromoting environment. In a previous study, we generated a monoclonal anti-ADAM17 antibody (A300E). Although showing no complement-dependent cytotoxicity or antibody-dependent cellular cytotoxicity, the antibody was rapidly internalized by ADAM17-expressing cells and was able to transport a conjugated toxin into target cells. As a result, doxorubicin-coupled A300E or Pseudomonas exotoxin A-loaded A300E was able to kill ADAM17-expressing cells. This eVect was strictly dependent on the presence of ADAM17 on the surface of target cells. As a proof of principle, both immunotoxins killed MDA-MB-231 breast cancer cells in an ADAM17-dependent manner. These data suggest that the use of anti-ADAM17 monoclonal antibodies as a carrier might be a promising new strategy for selective anti-cancer drug delivery.