Limits...
ODAM Expression Inhibits Human Breast Cancer Tumorigenesis.

Kestler DP, Foster JS, Bruker CT, Prenshaw JW, Kennel SJ, Wall JS, Weiss DT, Solomon A - Breast Cancer (Auckl) (2011)

Bottom Line: ODAM expression increased adhesion and apoptosis of the transfected MDA-MB-231 cells and suppressed their growth rate, migratory activity, and capability to invade extracellular matrix-coated membranes.Implantation of such cells into mouse mammary fat pads resulted in significantly smaller tumors than occurred in animals that received control cells; furthermore, ODAM-expressing cells, when injected intravenously into mice, failed to metastasize, whereas the control-transfected counterparts produced extensive lung lesions.Our finding that induction of ODAM expression in human breast cancer cells markedly inhibited their neoplastic properties provides further evidence for the regulatory role of this molecule in tumorigenesis and, consequently, is of potential clinical import.

View Article: PubMed Central - PubMed

Affiliation: Human Immunology and Cancer Program/Department of Medicine.

ABSTRACT
We have posited that Odontogenic Ameloblast Associated Protein (ODAM) serves as a novel prognostic biomarker in breast cancer and now have investigated its potential role in regulating tumor growth and metastasis. Human breast cancer MDA-MB-231 cells were transfected with a recombinant ODAM plasmid construct (or, as a control, the plasmid vector alone). ODAM expression increased adhesion and apoptosis of the transfected MDA-MB-231 cells and suppressed their growth rate, migratory activity, and capability to invade extracellular matrix-coated membranes. Implantation of such cells into mouse mammary fat pads resulted in significantly smaller tumors than occurred in animals that received control cells; furthermore, ODAM-expressing cells, when injected intravenously into mice, failed to metastasize, whereas the control-transfected counterparts produced extensive lung lesions. Our finding that induction of ODAM expression in human breast cancer cells markedly inhibited their neoplastic properties provides further evidence for the regulatory role of this molecule in tumorigenesis and, consequently, is of potential clinical import.

No MeSH data available.


Related in: MedlinePlus

ODAM expression suppresses development in mice of MDA-MB-231 lung metastases. A) Representative volume-rendered, dorsal view images of 18FLT accumulation (false colored green) in the lungs of 231-CON and 231-ODAM mice 31 days after intravenous injection of 8 × 105 cells. B) Representative hematoxylin/eosin-stained lung tissues from 231-CON and 231-ODAM injected mice (3 from each group, original magnifications, ×200).
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3091406&req=5

f7-bcbcr-2011-073: ODAM expression suppresses development in mice of MDA-MB-231 lung metastases. A) Representative volume-rendered, dorsal view images of 18FLT accumulation (false colored green) in the lungs of 231-CON and 231-ODAM mice 31 days after intravenous injection of 8 × 105 cells. B) Representative hematoxylin/eosin-stained lung tissues from 231-CON and 231-ODAM injected mice (3 from each group, original magnifications, ×200).

Mentions: In other experiments, groups of SCID mice were given intravenous injections of 8 × 105 ODAM-transfected or control MDA-MB-231 cells. By 31 days, the latter animals were in obvious distress due to extensive multinodular pulmonary metastases that were metabolically active, as evidenced by 18FLT micro-PET/CT scans (Fig. 7A). In contrast, those that received the 231-ODAM cells essentially had no lung lesions by imaging. The mean activities measured in 0.4 mm3 areas of interest in the lungs were 0.643 MBq/cm3 for 231-CON [n = 1] and 0.083 ± 0.062 MBq/cm3 [n = 3] for 231-ODAM recipients. In necropsy sections of mice receiving 231-ODAM cells only rare tumor deposits were found lodged in alveolar septal capillaries, with no evidence of invasion, and a complete lack of fibrosis, desmoplasia, or other host response (Fig. 7B).


ODAM Expression Inhibits Human Breast Cancer Tumorigenesis.

Kestler DP, Foster JS, Bruker CT, Prenshaw JW, Kennel SJ, Wall JS, Weiss DT, Solomon A - Breast Cancer (Auckl) (2011)

ODAM expression suppresses development in mice of MDA-MB-231 lung metastases. A) Representative volume-rendered, dorsal view images of 18FLT accumulation (false colored green) in the lungs of 231-CON and 231-ODAM mice 31 days after intravenous injection of 8 × 105 cells. B) Representative hematoxylin/eosin-stained lung tissues from 231-CON and 231-ODAM injected mice (3 from each group, original magnifications, ×200).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3091406&req=5

f7-bcbcr-2011-073: ODAM expression suppresses development in mice of MDA-MB-231 lung metastases. A) Representative volume-rendered, dorsal view images of 18FLT accumulation (false colored green) in the lungs of 231-CON and 231-ODAM mice 31 days after intravenous injection of 8 × 105 cells. B) Representative hematoxylin/eosin-stained lung tissues from 231-CON and 231-ODAM injected mice (3 from each group, original magnifications, ×200).
Mentions: In other experiments, groups of SCID mice were given intravenous injections of 8 × 105 ODAM-transfected or control MDA-MB-231 cells. By 31 days, the latter animals were in obvious distress due to extensive multinodular pulmonary metastases that were metabolically active, as evidenced by 18FLT micro-PET/CT scans (Fig. 7A). In contrast, those that received the 231-ODAM cells essentially had no lung lesions by imaging. The mean activities measured in 0.4 mm3 areas of interest in the lungs were 0.643 MBq/cm3 for 231-CON [n = 1] and 0.083 ± 0.062 MBq/cm3 [n = 3] for 231-ODAM recipients. In necropsy sections of mice receiving 231-ODAM cells only rare tumor deposits were found lodged in alveolar septal capillaries, with no evidence of invasion, and a complete lack of fibrosis, desmoplasia, or other host response (Fig. 7B).

Bottom Line: ODAM expression increased adhesion and apoptosis of the transfected MDA-MB-231 cells and suppressed their growth rate, migratory activity, and capability to invade extracellular matrix-coated membranes.Implantation of such cells into mouse mammary fat pads resulted in significantly smaller tumors than occurred in animals that received control cells; furthermore, ODAM-expressing cells, when injected intravenously into mice, failed to metastasize, whereas the control-transfected counterparts produced extensive lung lesions.Our finding that induction of ODAM expression in human breast cancer cells markedly inhibited their neoplastic properties provides further evidence for the regulatory role of this molecule in tumorigenesis and, consequently, is of potential clinical import.

View Article: PubMed Central - PubMed

Affiliation: Human Immunology and Cancer Program/Department of Medicine.

ABSTRACT
We have posited that Odontogenic Ameloblast Associated Protein (ODAM) serves as a novel prognostic biomarker in breast cancer and now have investigated its potential role in regulating tumor growth and metastasis. Human breast cancer MDA-MB-231 cells were transfected with a recombinant ODAM plasmid construct (or, as a control, the plasmid vector alone). ODAM expression increased adhesion and apoptosis of the transfected MDA-MB-231 cells and suppressed their growth rate, migratory activity, and capability to invade extracellular matrix-coated membranes. Implantation of such cells into mouse mammary fat pads resulted in significantly smaller tumors than occurred in animals that received control cells; furthermore, ODAM-expressing cells, when injected intravenously into mice, failed to metastasize, whereas the control-transfected counterparts produced extensive lung lesions. Our finding that induction of ODAM expression in human breast cancer cells markedly inhibited their neoplastic properties provides further evidence for the regulatory role of this molecule in tumorigenesis and, consequently, is of potential clinical import.

No MeSH data available.


Related in: MedlinePlus