Suvendu Das - Academia.edu (original) (raw)
Papers by Suvendu Das
Biochemical and Biophysical Research Communications, 2005
AK-5, a rat histiocytoma, is rejected in about 70% of the syngeneic animals when injected subcuta... more AK-5, a rat histiocytoma, is rejected in about 70% of the syngeneic animals when injected subcutaneously. The sera from the tumor rejecting animals possess a potent factor, referred to as serum factor (SF) that induces apoptosis in AK-5 tumor cells. In the present study, we show that treatment with SF or JAK/STAT inhibitors AG490 and Piceatannol induces apoptosis to a similar extent in BC-8 (a single cell clone of AK-5) cells. Our results demonstrate downregulation of a transcription factor, STAT3, as a critical regulator of SF-induced apoptosis in BC-8 cells. SF treatment enhanced the activity of NFjB, another transcription factor that regulates both proand antiapoptotic genes. The enhanced NFjB activity resulted in the elevation of TRAIL and its receptor DR4, both known to induce apoptosis. Activation of death receptors in turn enhances caspase-8 activity and stimulates the downstream pathways regulating BC-8 cell apoptosis. SF induced apoptosis in BC-8 cells mediated through downregulation of STAT3 and elevated NFjB activity is abrogated by treatment with MAPK inhibitors-PD98059 and SB203580. Our studies therefore indicate that modulation of MAPK activity plays a central role in SF-induced death signaling pathways in BC-8 cells.
Immunology Letters, 2002
Antigen dose is known to regulate T cell activation and anergy. Similarly, dose of antigen also r... more Antigen dose is known to regulate T cell activation and anergy. Similarly, dose of antigen also regulates NK cell lytic potential and phenotype development. Resident peritoneal cells of rat contain a small population of NK and NKT cells. Inoculation of AK-5 tumour cells intraperitoneally modulate the cytotoxic function of NK and NKT cells present in the peritoneal exudate cells (PEC) in a dose dependent manner. Low dose of tumour causes activation of NK and NKT cell cytotoxic function and enhanced NK and NKT cell population in PEC, whereas, high doses of tumour cause inactivation of NK and NKT cell cytotoxic function and depletion of the two sub-populations in the peritoneum. Different doses of tumour inoculation in the peritoneal cavity did not suppress the cytotoxic function of NK cells from spleen suggesting that a direct interaction between NK cells and tumour cells is required for the suppression of NK cell cytotoxic function. Tumour inoculation induced secretion of IL-2, IL-12, IFN-gamma and TNF-alpha by tumour infiltrating mononuclear cells (TIM) in ascitic fluid as well as in serum. The levels of IL-2, IL-12, IFN-gamma and TNF-alpha secretion were higher in animals, which rejected tumours as compared with the animals that failed to reject the tumours. Injection of anti IL-12 and anti IFN-gamma antibody reduced the survival rate of tumour injected animals, however, anti IL-2 antibody had no effect on the survival of animals. Following incubation with AK-5 tumour cells, activated NK cells upregulated perform expression, whereas, there was upregulation of CD95 expression in inactivated NK cells.
Cancer Immunology Immunotherapy, 2001
This study examines the eect of ®xed AK-5 tumour cells on rat NK cells. Co-culture of NK cells wi... more This study examines the eect of ®xed AK-5 tumour cells on rat NK cells. Co-culture of NK cells with ®xed tumour cells augmented the cytotoxicity of NK cells against NK-sensitive targets, YAC-1 and AK-5, and induced the secretion of IFN-c by NK cells. Antibody against IFN-c suppressed the anti-tumour activity of NK cells, whereas the addition of T cells during co-culture enhanced this activity. However, macrophages and B cells had no signi®cant eect when present during co-culture with NK cells. All the inducible cytotoxicity was contained within the NK (CD161 + ) and NKT (CD3 + , CD161 + ) subsets of lymphocytes. However, in the presence of T cells, the cytolytic potential of NKT cells was higher than that of NK cells alone. The augmentation of cytotoxic activity of NK cells by AK-5 cells in presence of T cells was dependent on IL-2 and IFN-c secretion. NK cell activation was blocked by speci®c antibodies to IL-2 and IFN-c in the presence of T cells. Interaction between ®xed AK-5 cells with NK and T cell populations induced the expression of Fas-L and perforin in NK cells. These data demonstrate that ®xed AK-5 cells initiated cytokine synthesis by NK cells, and the enhanced cytotoxic activity in the presence of T cells was induced as a consequence of the products secreted by activated T lymphocytes. The present observations re¯ect the possible interactions taking place in vivo after the transplantation of AK-5 tumour in animals. They also suggest direct activation of NK cells after their interaction with the tumour cells.
Cancer research, 2010
The lymphatic system is an important pathway for tumor dissemination to the lymph nodes, but to w... more The lymphatic system is an important pathway for tumor dissemination to the lymph nodes, but to which extent it contributes to the formation of distant metastases remains unknown. We report that induction of lymphangiogenesis by vascular endothelial growth factor-C (VEGF-C) at the secondary site, in the lung, facilitates expansion of already disseminated cancer cells throughout the lung tissue. By using orthotopic spontaneous metastasis models in nude mice, we show that VEGF-C expression by tumor cells altered the pattern of pulmonary metastases from nodular to diffuse and facilitated disease progression. Metastases expressing VEGF-C were tightly associated with the airways, in contrast to the control cells that were scattered in the lung parenchyma, throughout the alveolar region. VEGF-C induced lung lymphangiogenesis and promoted intralymphatic spread of metastases in the lung and formation of tumor emboli in the pulmonary arteries. This pattern of metastasis corresponds to lymphangitic carcinomatosis metastatic phenotype in human cancer patients, an extremely aggressive pattern of pulmonary metastases. In accordance, pulmonary breast cancer metastases from patients which were classified as lymphangitic carcinomatosis showed high levels of VEGF-C expression in cancer cells. These data show that VEGF-C promotes late steps of the metastatic process and identify the VEGF-C/VEGF receptor-3 pathway as the target not only for prevention of metastases, but also for treatment of established metastatic disease.
European Journal of Immunology, 2004
DC are the most efficient antigen-presenting cells that regulate the immune response. Here, we de... more DC are the most efficient antigen-presenting cells that regulate the immune response. Here, we demonstrate the expression of NK cell receptor protein-2 (NKR-P2) on rat and mouse DC, and we show that NKR-P2 gets reorganized upon antigen contact. DC activated with anti-NKR-P2 mAb exhibit enhanced apoptotic killing of tumor targets, whereas blocking the interaction between NKR-P2 and its ligand with rNKR-P2 abrogated apoptotic killing, suggesting NKR-P2 to function as an activating molecule on DC. In vivo injection of anti-NKR-P2 mAb augmented DC activity and delayed tumor progression. NKR-P2 signaling involved Ca 2+ influx, culminating in the expression of the apoptosis-inducing molecule, TNF- § . Taken together, these observations suggest that NKR-P2 (the rat orthologue of human NKG2D) acts as a target-recognition molecule on DC.
Annals of The New York Academy of Sciences, 2008
Most cancerous lesions metastasize through the lymphatic system and the status of regional lymph ... more Most cancerous lesions metastasize through the lymphatic system and the status of regional lymph nodes is the most important indicator of a patient's prognosis. The extent of lymph node involvement with cancer is also an important parameter used for determining treatment options. Although the importance of the lymphatic system for metastasis has been well recognized, traditionally, the lymphatic vessels have not been considered actively involved in the metastatic process. Recent evidence, however, indicates that the activation of the lymphatic system is an important factor in tumor progression to metastasis. Tumor lymphangiogenesis has been associated with increased propensity for metastasis, and lymphatic vessel density has emerged as another promising prognostic indicator. More recently, lymphangiogenesis in the sentinel lymph nodes has been shown to contribute to malignant progression. In addition to its role as a transport system for tumor cells, the lymphatic system may also be more actively involved in metastases by directly facilitating tumor cell recruitment into the lymphatic vessels. This review highlights recent advances in our understanding of the mechanisms by which lymphatic vessels participate in metastasis.
Biochemical and Biophysical Research Communications, 2005
AK-5, a rat histiocytoma, is rejected in about 70% of the syngeneic animals when injected subcuta... more AK-5, a rat histiocytoma, is rejected in about 70% of the syngeneic animals when injected subcutaneously. The sera from the tumor rejecting animals possess a potent factor, referred to as serum factor (SF) that induces apoptosis in AK-5 tumor cells. In the present study, we show that treatment with SF or JAK/STAT inhibitors AG490 and Piceatannol induces apoptosis to a similar extent in BC-8 (a single cell clone of AK-5) cells. Our results demonstrate downregulation of a transcription factor, STAT3, as a critical regulator of SF-induced apoptosis in BC-8 cells. SF treatment enhanced the activity of NFjB, another transcription factor that regulates both proand antiapoptotic genes. The enhanced NFjB activity resulted in the elevation of TRAIL and its receptor DR4, both known to induce apoptosis. Activation of death receptors in turn enhances caspase-8 activity and stimulates the downstream pathways regulating BC-8 cell apoptosis. SF induced apoptosis in BC-8 cells mediated through downregulation of STAT3 and elevated NFjB activity is abrogated by treatment with MAPK inhibitors-PD98059 and SB203580. Our studies therefore indicate that modulation of MAPK activity plays a central role in SF-induced death signaling pathways in BC-8 cells.
Immunology Letters, 2002
Antigen dose is known to regulate T cell activation and anergy. Similarly, dose of antigen also r... more Antigen dose is known to regulate T cell activation and anergy. Similarly, dose of antigen also regulates NK cell lytic potential and phenotype development. Resident peritoneal cells of rat contain a small population of NK and NKT cells. Inoculation of AK-5 tumour cells intraperitoneally modulate the cytotoxic function of NK and NKT cells present in the peritoneal exudate cells (PEC) in a dose dependent manner. Low dose of tumour causes activation of NK and NKT cell cytotoxic function and enhanced NK and NKT cell population in PEC, whereas, high doses of tumour cause inactivation of NK and NKT cell cytotoxic function and depletion of the two sub-populations in the peritoneum. Different doses of tumour inoculation in the peritoneal cavity did not suppress the cytotoxic function of NK cells from spleen suggesting that a direct interaction between NK cells and tumour cells is required for the suppression of NK cell cytotoxic function. Tumour inoculation induced secretion of IL-2, IL-12, IFN-gamma and TNF-alpha by tumour infiltrating mononuclear cells (TIM) in ascitic fluid as well as in serum. The levels of IL-2, IL-12, IFN-gamma and TNF-alpha secretion were higher in animals, which rejected tumours as compared with the animals that failed to reject the tumours. Injection of anti IL-12 and anti IFN-gamma antibody reduced the survival rate of tumour injected animals, however, anti IL-2 antibody had no effect on the survival of animals. Following incubation with AK-5 tumour cells, activated NK cells upregulated perform expression, whereas, there was upregulation of CD95 expression in inactivated NK cells.
Cancer Immunology Immunotherapy, 2001
This study examines the eect of ®xed AK-5 tumour cells on rat NK cells. Co-culture of NK cells wi... more This study examines the eect of ®xed AK-5 tumour cells on rat NK cells. Co-culture of NK cells with ®xed tumour cells augmented the cytotoxicity of NK cells against NK-sensitive targets, YAC-1 and AK-5, and induced the secretion of IFN-c by NK cells. Antibody against IFN-c suppressed the anti-tumour activity of NK cells, whereas the addition of T cells during co-culture enhanced this activity. However, macrophages and B cells had no signi®cant eect when present during co-culture with NK cells. All the inducible cytotoxicity was contained within the NK (CD161 + ) and NKT (CD3 + , CD161 + ) subsets of lymphocytes. However, in the presence of T cells, the cytolytic potential of NKT cells was higher than that of NK cells alone. The augmentation of cytotoxic activity of NK cells by AK-5 cells in presence of T cells was dependent on IL-2 and IFN-c secretion. NK cell activation was blocked by speci®c antibodies to IL-2 and IFN-c in the presence of T cells. Interaction between ®xed AK-5 cells with NK and T cell populations induced the expression of Fas-L and perforin in NK cells. These data demonstrate that ®xed AK-5 cells initiated cytokine synthesis by NK cells, and the enhanced cytotoxic activity in the presence of T cells was induced as a consequence of the products secreted by activated T lymphocytes. The present observations re¯ect the possible interactions taking place in vivo after the transplantation of AK-5 tumour in animals. They also suggest direct activation of NK cells after their interaction with the tumour cells.
Cancer research, 2010
The lymphatic system is an important pathway for tumor dissemination to the lymph nodes, but to w... more The lymphatic system is an important pathway for tumor dissemination to the lymph nodes, but to which extent it contributes to the formation of distant metastases remains unknown. We report that induction of lymphangiogenesis by vascular endothelial growth factor-C (VEGF-C) at the secondary site, in the lung, facilitates expansion of already disseminated cancer cells throughout the lung tissue. By using orthotopic spontaneous metastasis models in nude mice, we show that VEGF-C expression by tumor cells altered the pattern of pulmonary metastases from nodular to diffuse and facilitated disease progression. Metastases expressing VEGF-C were tightly associated with the airways, in contrast to the control cells that were scattered in the lung parenchyma, throughout the alveolar region. VEGF-C induced lung lymphangiogenesis and promoted intralymphatic spread of metastases in the lung and formation of tumor emboli in the pulmonary arteries. This pattern of metastasis corresponds to lymphangitic carcinomatosis metastatic phenotype in human cancer patients, an extremely aggressive pattern of pulmonary metastases. In accordance, pulmonary breast cancer metastases from patients which were classified as lymphangitic carcinomatosis showed high levels of VEGF-C expression in cancer cells. These data show that VEGF-C promotes late steps of the metastatic process and identify the VEGF-C/VEGF receptor-3 pathway as the target not only for prevention of metastases, but also for treatment of established metastatic disease.
European Journal of Immunology, 2004
DC are the most efficient antigen-presenting cells that regulate the immune response. Here, we de... more DC are the most efficient antigen-presenting cells that regulate the immune response. Here, we demonstrate the expression of NK cell receptor protein-2 (NKR-P2) on rat and mouse DC, and we show that NKR-P2 gets reorganized upon antigen contact. DC activated with anti-NKR-P2 mAb exhibit enhanced apoptotic killing of tumor targets, whereas blocking the interaction between NKR-P2 and its ligand with rNKR-P2 abrogated apoptotic killing, suggesting NKR-P2 to function as an activating molecule on DC. In vivo injection of anti-NKR-P2 mAb augmented DC activity and delayed tumor progression. NKR-P2 signaling involved Ca 2+ influx, culminating in the expression of the apoptosis-inducing molecule, TNF- § . Taken together, these observations suggest that NKR-P2 (the rat orthologue of human NKG2D) acts as a target-recognition molecule on DC.
Annals of The New York Academy of Sciences, 2008
Most cancerous lesions metastasize through the lymphatic system and the status of regional lymph ... more Most cancerous lesions metastasize through the lymphatic system and the status of regional lymph nodes is the most important indicator of a patient's prognosis. The extent of lymph node involvement with cancer is also an important parameter used for determining treatment options. Although the importance of the lymphatic system for metastasis has been well recognized, traditionally, the lymphatic vessels have not been considered actively involved in the metastatic process. Recent evidence, however, indicates that the activation of the lymphatic system is an important factor in tumor progression to metastasis. Tumor lymphangiogenesis has been associated with increased propensity for metastasis, and lymphatic vessel density has emerged as another promising prognostic indicator. More recently, lymphangiogenesis in the sentinel lymph nodes has been shown to contribute to malignant progression. In addition to its role as a transport system for tumor cells, the lymphatic system may also be more actively involved in metastases by directly facilitating tumor cell recruitment into the lymphatic vessels. This review highlights recent advances in our understanding of the mechanisms by which lymphatic vessels participate in metastasis.