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Metastasizing, Luciferase Transduced MAT‑Lu Rat Prostate Cancer Models: Follow up of Bolus and Metronomic Therapy with Doxorubicin as Model Drug.

Jantscheff P, Esser N, Geipel A, Woias P, Ziroli V, Goldschmidtboing F, Massing U - Cancers (Basel) (2011)

Bottom Line: Our sensitive method, however, for the first time detects metastasis also in lymph node (11/24), spleen (3/24), kidney (4/24), liver (5/24), and bone tissue (femur or spinal cord - 5/20 and 12/20, respectively).Intravenous bolus treatment of MAT-Lu PCa with doxorubicin reduced subcutaneous tumor growth by about 50% and the number of animals affected by metastatic lesions in lymph nodes (0/4), lung (3/6) or lumbar spine (0/2), as determined by in vivo imaging and in vitro analysis.Additionally, the possible applicability of the luciferase transduced MAT-Lu model(s) to study basic principles of metronomic therapies via jugular vein catheter, using newly established active microport pumping systems, is presented.

View Article: PubMed Central - PubMed

Affiliation: Tumour Biology Center, Clinical Research, Department Lipids & Liposomes, Breisacher Str.117, D-79106 Freiburg, Germany. jantscheff@tumorbio.uni-freiburg.de.

ABSTRACT
The most fatal outcomes of prostate carcinoma (PCa) result from hormone-refractory variants of the tumor, especially from metastatic spread rather than from primary tumor burden. The goal of the study was to establish and apply rat MAT-Lu prostate cancer tumor models for improved non-invasive live follow up of tumor growth and metastasis by in vivo bioluminescence. We established luciferase transduced MAT-Lu rat PCa cells and studied tumor growth and metastatic processes in an ectopic as well as orthotopic setting. An intravenous bolus treatment with doxorubicin was used to demonstrate the basic applicability of in vivo imaging to follow up therapeutic intervention in these models. In vitro analysis of tissue homogenates confirmed major metastatic spread of subcutaneous tumors into the lung. Our sensitive method, however, for the first time detects metastasis also in lymph node (11/24), spleen (3/24), kidney (4/24), liver (5/24), and bone tissue (femur or spinal cord - 5/20 and 12/20, respectively). Preliminary data of orthotopic implantation (three animals) showed metastatic invasion to investigated organs in all animals but with varying preference (e.g., to lymph nodes). Intravenous bolus treatment of MAT-Lu PCa with doxorubicin reduced subcutaneous tumor growth by about 50% and the number of animals affected by metastatic lesions in lymph nodes (0/4), lung (3/6) or lumbar spine (0/2), as determined by in vivo imaging and in vitro analysis. Additionally, the possible applicability of the luciferase transduced MAT-Lu model(s) to study basic principles of metronomic therapies via jugular vein catheter, using newly established active microport pumping systems, is presented.

No MeSH data available.


Related in: MedlinePlus

Metastatic burden in different rat tissues compared to luciferase activity in MAT-Lu ELN cells. Metastatic burden in individual tissues was determined by homogenization and subsequent luciferase assay. Metastases appear in lung, lymph nodes, spleen, kidney, liver, and bone tissue (femur or lumbar spine) of untreated animals (columns). The metastatic burden in respective tissues (columns) is shown at the y-axis as mean RLU (relative light unit) values of tissues from metastatic animals. Corresponding cell numbers were calculated by a standard curve of crude lysates from defined numbers of MAT-Lu ELN cells (□) numbered on the x-axis. The black horizontal line marks the detection limit for metastatic lesions in individual tissues which was about 100 cells per tissue piece when defined as ≥ 1.6 times of the background value (■).
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f2-cancers-03-02679: Metastatic burden in different rat tissues compared to luciferase activity in MAT-Lu ELN cells. Metastatic burden in individual tissues was determined by homogenization and subsequent luciferase assay. Metastases appear in lung, lymph nodes, spleen, kidney, liver, and bone tissue (femur or lumbar spine) of untreated animals (columns). The metastatic burden in respective tissues (columns) is shown at the y-axis as mean RLU (relative light unit) values of tissues from metastatic animals. Corresponding cell numbers were calculated by a standard curve of crude lysates from defined numbers of MAT-Lu ELN cells (□) numbered on the x-axis. The black horizontal line marks the detection limit for metastatic lesions in individual tissues which was about 100 cells per tissue piece when defined as ≥ 1.6 times of the background value (■).

Mentions: Despite the failure to detect metastases by in vivo imaging, the transduction of MAT-Lu cells allowed highly sensitive tumor cell detection in vitro in tissue homogenates by subsequent luciferase assay [13,24], even in lung tissue with no macroscopically visible metastasis. These data not only show (Figure 2: columns) the typical metastatic infiltration of the lung by subcutaneous MAT-Lu PCa cells (13/24), but metastatic lesions could also be detected in inguinal lymph nodes (11/24), spleen (3/24), kidney (4/24), liver (5/24), and bone tissue (femur or lumbar spine - 5/20 and 12/20, respectively). In all these latter tissues, however, no metastases were ever visible. This was not surprising since metastatic burden of the latter tissues, corresponding to 2,000–6,000 metastatic cells, was only ≤1/10–1/100 of the lung (70,000–120,000 metastatic cells) (Figure 2: curve) in the individual tissues, as shown by the significantly lower RLU (relative light unit) values (Figure 2: columns).


Metastasizing, Luciferase Transduced MAT‑Lu Rat Prostate Cancer Models: Follow up of Bolus and Metronomic Therapy with Doxorubicin as Model Drug.

Jantscheff P, Esser N, Geipel A, Woias P, Ziroli V, Goldschmidtboing F, Massing U - Cancers (Basel) (2011)

Metastatic burden in different rat tissues compared to luciferase activity in MAT-Lu ELN cells. Metastatic burden in individual tissues was determined by homogenization and subsequent luciferase assay. Metastases appear in lung, lymph nodes, spleen, kidney, liver, and bone tissue (femur or lumbar spine) of untreated animals (columns). The metastatic burden in respective tissues (columns) is shown at the y-axis as mean RLU (relative light unit) values of tissues from metastatic animals. Corresponding cell numbers were calculated by a standard curve of crude lysates from defined numbers of MAT-Lu ELN cells (□) numbered on the x-axis. The black horizontal line marks the detection limit for metastatic lesions in individual tissues which was about 100 cells per tissue piece when defined as ≥ 1.6 times of the background value (■).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3757437&req=5

f2-cancers-03-02679: Metastatic burden in different rat tissues compared to luciferase activity in MAT-Lu ELN cells. Metastatic burden in individual tissues was determined by homogenization and subsequent luciferase assay. Metastases appear in lung, lymph nodes, spleen, kidney, liver, and bone tissue (femur or lumbar spine) of untreated animals (columns). The metastatic burden in respective tissues (columns) is shown at the y-axis as mean RLU (relative light unit) values of tissues from metastatic animals. Corresponding cell numbers were calculated by a standard curve of crude lysates from defined numbers of MAT-Lu ELN cells (□) numbered on the x-axis. The black horizontal line marks the detection limit for metastatic lesions in individual tissues which was about 100 cells per tissue piece when defined as ≥ 1.6 times of the background value (■).
Mentions: Despite the failure to detect metastases by in vivo imaging, the transduction of MAT-Lu cells allowed highly sensitive tumor cell detection in vitro in tissue homogenates by subsequent luciferase assay [13,24], even in lung tissue with no macroscopically visible metastasis. These data not only show (Figure 2: columns) the typical metastatic infiltration of the lung by subcutaneous MAT-Lu PCa cells (13/24), but metastatic lesions could also be detected in inguinal lymph nodes (11/24), spleen (3/24), kidney (4/24), liver (5/24), and bone tissue (femur or lumbar spine - 5/20 and 12/20, respectively). In all these latter tissues, however, no metastases were ever visible. This was not surprising since metastatic burden of the latter tissues, corresponding to 2,000–6,000 metastatic cells, was only ≤1/10–1/100 of the lung (70,000–120,000 metastatic cells) (Figure 2: curve) in the individual tissues, as shown by the significantly lower RLU (relative light unit) values (Figure 2: columns).

Bottom Line: Our sensitive method, however, for the first time detects metastasis also in lymph node (11/24), spleen (3/24), kidney (4/24), liver (5/24), and bone tissue (femur or spinal cord - 5/20 and 12/20, respectively).Intravenous bolus treatment of MAT-Lu PCa with doxorubicin reduced subcutaneous tumor growth by about 50% and the number of animals affected by metastatic lesions in lymph nodes (0/4), lung (3/6) or lumbar spine (0/2), as determined by in vivo imaging and in vitro analysis.Additionally, the possible applicability of the luciferase transduced MAT-Lu model(s) to study basic principles of metronomic therapies via jugular vein catheter, using newly established active microport pumping systems, is presented.

View Article: PubMed Central - PubMed

Affiliation: Tumour Biology Center, Clinical Research, Department Lipids & Liposomes, Breisacher Str.117, D-79106 Freiburg, Germany. jantscheff@tumorbio.uni-freiburg.de.

ABSTRACT
The most fatal outcomes of prostate carcinoma (PCa) result from hormone-refractory variants of the tumor, especially from metastatic spread rather than from primary tumor burden. The goal of the study was to establish and apply rat MAT-Lu prostate cancer tumor models for improved non-invasive live follow up of tumor growth and metastasis by in vivo bioluminescence. We established luciferase transduced MAT-Lu rat PCa cells and studied tumor growth and metastatic processes in an ectopic as well as orthotopic setting. An intravenous bolus treatment with doxorubicin was used to demonstrate the basic applicability of in vivo imaging to follow up therapeutic intervention in these models. In vitro analysis of tissue homogenates confirmed major metastatic spread of subcutaneous tumors into the lung. Our sensitive method, however, for the first time detects metastasis also in lymph node (11/24), spleen (3/24), kidney (4/24), liver (5/24), and bone tissue (femur or spinal cord - 5/20 and 12/20, respectively). Preliminary data of orthotopic implantation (three animals) showed metastatic invasion to investigated organs in all animals but with varying preference (e.g., to lymph nodes). Intravenous bolus treatment of MAT-Lu PCa with doxorubicin reduced subcutaneous tumor growth by about 50% and the number of animals affected by metastatic lesions in lymph nodes (0/4), lung (3/6) or lumbar spine (0/2), as determined by in vivo imaging and in vitro analysis. Additionally, the possible applicability of the luciferase transduced MAT-Lu model(s) to study basic principles of metronomic therapies via jugular vein catheter, using newly established active microport pumping systems, is presented.

No MeSH data available.


Related in: MedlinePlus