Mechanisms of Paraneoplastic Syndromes in Mice Bearing a Spontaneous Lung Adenocarcinoma

Abstract

Paraneoplastic syndromes are rarely described in animal models. It may be useful to have a suitable experimental model to study the mechanisms by which they are produced. In this study, we describe a murine lung adenocarcinoma, P07, which presents hypercalcemia, leukocytosis and cachexia. We determined the presence of PTHrP in plasma as well as GM-CSF produced by P07 cells. TNF-α, which is responsible for cachexia, could neither be detected in serum nor in P07 cell supernatants. We conclude that this model, which shows paraneoplastic syndromes similar to those of lung tumor patients, should be useful to study the pathways and significance of these signs.

Reduction of tumor progression and paraneoplastic syndrome development in murine lung adenocarcinoma by nonsteroidal antiinflammatory drugs

“…These factors are thought to play key roles in the development of such symptoms. 22 Inflammatory responses, when they become systemic and sustained, may enhance tumor growth, metastasis outcome and paraneoplastic syndrome development.…”

“…[3][4][5] Our rationale for NSAID use was to treat tumor-associated syndromes given that inflammatory components (GM-CSF, IL-6, leukocytosis) are present along tumor progression. 22 Moreover, the role of eicosanoids in the settlement and progression of cancer cachexia has been documented, making NSAID treatment a good approach to deal with this syndrome. 19,26 Treatment with both NSAIDs delayed LP07 s.c. tumor growth (Fig.…”

Reduction of tumor progression and paraneoplastic syndrome development in murine lung adenocarcinoma by nonsteroidal antiinflammatory drugs

“…These factors are thought to play key roles in the development of such symptoms. 22 Inflammatory responses, when they become systemic and sustained, may enhance tumor growth, metastasis outcome and paraneoplastic syndrome development.…”

“…[3][4][5] Our rationale for NSAID use was to treat tumor-associated syndromes given that inflammatory components (GM-CSF, IL-6, leukocytosis) are present along tumor progression. 22 Moreover, the role of eicosanoids in the settlement and progression of cancer cachexia has been documented, making NSAID treatment a good approach to deal with this syndrome. 19,26 Treatment with both NSAIDs delayed LP07 s.c. tumor growth (Fig.…”

Differential Response of Myeloid-Derived Suppressor Cells to the Nonsteroidal Anti-Inflammatory Agent Indomethacin in Tumor-Associated and Tumor-Free Microenvironments

“…The LP07 lung adenocarcinoma secretes GM-CSF, IL-6, IL-1b, parathyroid hormone-related peptide (PTHrP), and PGE 2 , which together contribute to generate a systemic inflammatory response in tumor-bearing mice (23,30). Because these soluble factors can promote the expansion of MDSCs (4,31) and IND treatment suppresses tumor progression (Supplemental Fig.…”

Long-Term Adaptation of Lung Tumor Cell Lines with Increasing Concentrations of Nitric Oxide Donor

“…All media and supplements were purchased from Invitrogen (California, USA), except where noted. A549, a human lung adenocarcinoma cell line [23,24], and LP07, a mouse lung adenocarcinoma cell line [25][26][27], were used in this study. The A549 cell line was purchased from American Type Culture Collection (Virginia, USA); the LP07 cell line was previously obtained as a generous gift from Dr. Slobodanka Klein at the University of Buenos Aires, Argentina.…”

Reduction of tumor progression and paraneoplastic syndrome development in murine lung adenocarcinoma by nonsteroidal antiinflammatory drugs

“…These factors are thought to play key roles in the development of such symptoms. 22 Inflammatory responses, when they become systemic and sustained, may enhance tumor growth, metastasis outcome and paraneoplastic syndrome development.…”

“…[3][4][5] Our rationale for NSAID use was to treat tumor-associated syndromes given that inflammatory components (GM-CSF, IL-6, leukocytosis) are present along tumor progression. 22 Moreover, the role of eicosanoids in the settlement and progression of cancer cachexia has been documented, making NSAID treatment a good approach to deal with this syndrome. 19,26 Treatment with both NSAIDs delayed LP07 s.c. tumor growth (Fig.…”

Differential Response of Myeloid-Derived Suppressor Cells to the Nonsteroidal Anti-Inflammatory Agent Indomethacin in Tumor-Associated and Tumor-Free Microenvironments

“…The LP07 lung adenocarcinoma secretes GM-CSF, IL-6, IL-1b, parathyroid hormone-related peptide (PTHrP), and PGE 2 , which together contribute to generate a systemic inflammatory response in tumor-bearing mice (23,30). Because these soluble factors can promote the expansion of MDSCs (4,31) and IND treatment suppresses tumor progression (Supplemental Fig.…”

Long-Term Adaptation of Lung Tumor Cell Lines with Increasing Concentrations of Nitric Oxide Donor

“…All media and supplements were purchased from Invitrogen (California, USA), except where noted. A549, a human lung adenocarcinoma cell line [23,24], and LP07, a mouse lung adenocarcinoma cell line [25][26][27], were used in this study. The A549 cell line was purchased from American Type Culture Collection (Virginia, USA); the LP07 cell line was previously obtained as a generous gift from Dr. Slobodanka Klein at the University of Buenos Aires, Argentina.…”

Reduction of tumor progression and paraneoplastic syndrome development in murine lung adenocarcinoma by nonsteroidal antiinflammatory drugs

“…These factors are thought to play key roles in the development of such symptoms. 22 Inflammatory responses, when they become systemic and sustained, may enhance tumor growth, metastasis outcome and paraneoplastic syndrome development.…”

“…[3][4][5] Our rationale for NSAID use was to treat tumor-associated syndromes given that inflammatory components (GM-CSF, IL-6, leukocytosis) are present along tumor progression. 22 Moreover, the role of eicosanoids in the settlement and progression of cancer cachexia has been documented, making NSAID treatment a good approach to deal with this syndrome. 19,26 Treatment with both NSAIDs delayed LP07 s.c. tumor growth (Fig.…”

Differential Response of Myeloid-Derived Suppressor Cells to the Nonsteroidal Anti-Inflammatory Agent Indomethacin in Tumor-Associated and Tumor-Free Microenvironments

“…The LP07 lung adenocarcinoma secretes GM-CSF, IL-6, IL-1b, parathyroid hormone-related peptide (PTHrP), and PGE 2 , which together contribute to generate a systemic inflammatory response in tumor-bearing mice (23,30). Because these soluble factors can promote the expansion of MDSCs (4,31) and IND treatment suppresses tumor progression (Supplemental Fig.…”

Long-Term Adaptation of Lung Tumor Cell Lines with Increasing Concentrations of Nitric Oxide Donor

“…All media and supplements were purchased from Invitrogen (California, USA), except where noted. A549, a human lung adenocarcinoma cell line [23,24], and LP07, a mouse lung adenocarcinoma cell line [25][26][27], were used in this study. The A549 cell line was purchased from American Type Culture Collection (Virginia, USA); the LP07 cell line was previously obtained as a generous gift from Dr. Slobodanka Klein at the University of Buenos Aires, Argentina.…”