Osteopontin Induction of Hyaluronan Synthase 2 Expression Promotes Breast Cancer Malignancy

Osteopontin (OPN) is a tumor-associated, secreted phosphoprotein that has been implicated in breast cancer progression and metastasis. Research concerning how OPN functions in tumor progression has led to the identification of a limited number of genes that contribute functionally to OPN-induced cellular behaviors. Recent microarray analysis, comparing 21NT breast cancer cells transfected to constitutively overexpress OPN with control cells, revealed hyaluronan synthase 2 (HAS2) to be a gene highly up-regulated in OPN-overexpressing cells. In this study, we further examined the relationship between OPN and HAS2. We show that 21NT cells of is with and and is tumor to cells and of 21NT cells OPN in a in and of in a in cellular and in this is the of the of OPN to and in breast cancer cells and further a relationship behaviors. Osteopontin (OPN) is a tumor-associated, secreted phosphoprotein that has been implicated in breast cancer progression and metastasis. Research concerning how OPN functions in tumor progression has led to the identification of a limited number of genes that contribute functionally to OPN-induced cellular behaviors. Recent microarray analysis, comparing 21NT breast cancer cells transfected to constitutively overexpress OPN with control cells, revealed hyaluronan synthase 2 (HAS2) to be a gene highly up-regulated in OPN-overexpressing cells. In this study, we further examined the relationship between OPN and HAS2. We show that 21NT cells of is with and and is tumor to cells and of 21NT cells OPN in a in and of in a in cellular and in this is the of the of OPN to and in breast cancer cells and further a relationship behaviors. has a in tumor and tumor cells with the and and a and that behaviors. a that to the of (OPN) hyaluronan hyaluronan is that has been implicated in the progression and of breast OPN has been to with and in with breast in with breast cancer of the OPN functionally to OPN is to to and of the OPN-induced has been to cellular functions and OPN has been in to to the of a limited number been genes that contribute to OPN-induced microarray to the between 21NT control and breast cancer cells We genes OPN the of and genes the and we hyaluronan synthase 2 (HAS2) a gene highly up-regulated is a of of and is in the of and has been with progression of a of tumor and tumor progression is has been to be to to to with and to and is is of of the gene and is the of of of and the of of that contribute to tumor progression and metastasis. in cells in cancer cells to tumor in In of the of cells in of in cancer cells to to cells, of in breast cancer cells and tumor this study, we and in cells constitutively OPN behaviors. we show that of OPN in a to and to and to cells. We show that of in cells in and of the of a relationship between OPN and in the of breast and in cells the 21NT with a a OPN of OPN the 21NT cells in in OPN and to transfected cells to the highly is to of cells of the of OPN in the control cells of the of OPN a of of cells with the to a and in with of the cells in a of and OPN and to the the analysis, and of to a of in a and and of gene the with and OPN and and and and and and to a of in and further in to the to the with the of the in a of and of of of the and and OPN and of and and of of the in in with gene of a and the of the the is to be the the of the and of the a the of the and to a of a in to in the with gene of of the the of the and of in gene the of the gene of to the the of the to the control the cells in in and to and the cells in the of in and of in with to and to cells a with the the the of cells and the and of the to of of of of of in in a number cells in in and to to cells with to and the to and and in a of the examined in to the and the of comparing the of to a of and to in with 2 of a of with the and to in a cells and to a of of a of with the and cells, the and to in a of to cells to with the of a of of cells with and in with a of and to the of the the cells in and with the between the with the of the with control and cells in in and to cells to the and to to cells in in a in cells in and to a of cells with the of with the of the with and of tumor cells and to cells with of cells in of and and in a and of the with of and control a of of the the the of the the and in the 21NT cells transfected with in to the cells to in and to with and and to transfected of in the of OPN and and and with in and of the cells in the of a cells and number a of in microarray 21NT control 21NT cells to genes OPN genes up-regulated OPN the gene we is of of the gene we to the of to the of in the 21NT cells. that is the highly up-regulated in the 21NT cells, with in to control cells is with microarray revealed a in in between to and of that with we a to the of secreted the 21NT 21NT cells with of of has been to in we a of to the and the 21NT cells. In this the cells with a of the and of the a a We in the 21NT cells, with a in with that that of we the cells with to the of the 21NT cells, and that cells secreted a of 21NT control transfected cells and 21NT cells with a of the cells of the 21NT cells with the of the of of the 21NT control and cells with cells to the and the of the to the of is to of cells with the of secreted and in the cells, further in cells to of 21NT is a of of cells. that of and of tumor cells in that the of in the 21NT cells the of cells in this we 21NT control and cells in and to In with of we that the cells and with control transfected cells, to in and of 21NT cells in of the 21NT control and cells and cells with in of with and the number of number of is the number of cells OPN to with of cells with the of the 21NT cells we 21NT cells in in the of of to with with the of of 21NT cells with in and of of 21NT to has been to the of breast and cancer cells to a in to the We the of 21NT control and cells to to and that 21NT cells OPN with control cells this is and cells with and to to with of 21NT cells to control cells in to a in this cellular of 21NT cells to 21NT cells with and to of cells to cells and cells in cells and and of the and cells and to with control cells and of tumor to 21NT control and with and to cells cells and a 21NT cells OPN to with control cells, and of the this of in the of of in the cells, we transfected the 21NT and revealed a in in the cells, in the control the cells that the in the cells to a of we examined OPN and in in the cells a in of OPN in the of and OPN in cells. of of OPN cells and and gene and to the 21NT control 21NT control cells 21NT OPN transfected 21NT OPN cells in and of of secreted we revealed of between the 21NT OPN-overexpressing transfected with control and the cells 21NT OPN-overexpressing we examined in of the of the with with in between control and in secreted and the in with the of in cells. of to secreted is cells of cells transfected the 21NT control 21NT OPN control 21NT OPN cells of in in of the transfected examined a the 21NT OPN-overexpressing cells and transfected control cells the transfected cells of of and in transfected cells a of cells in of a cells and cells a the of cells. of in a of and the number of the the of of 21NT OPN-overexpressing the in functionally we the of the cells in of in the cells in a in the of cells in with and control is a secreted phosphoprotein that has been to the progression of the OPN functions to been In this study, we that of OPN in the 21NT breast cancer in and of in cells to and to of in 21NT OPN-overexpressing cells led to a in and and a in in and in of and a OPN in breast of a of has been to a in the and of tumor breast and has been to contribute to and of and cells and to the of and breast cancer cells that cells OPN is in with in with of breast cancer cells OPN to to is a to the a of OPN in to the of and OPN has been of a gene is of OPN in breast cancer cells has been to in the that of OPN-overexpressing cells is of a that is with the of in tumor a of and has been to of and breast cancer cells to and in this has been to be in is that the in and 21NT OPN-overexpressing cells the and of the OPN a breast cancer cells OPN and to the of of a in the of breast cancer cells to in this is of the cells to the of control cells, that OPN be in the 21NT tumor to tumor show that cells OPN to in with and that of this of tumor cells to in has been to the of the OPN is to the of breast tumor cells and to of and OPN to in that of OPN in and in of has been to the of cancer to been to the to and the in the and of breast cancer cells constitutively OPN further a in the of in to and to OPN and the of in cells constitutively we a to show that the of in a in led to a in and the to the the in has been and in in cancer cells a in with the of in is to in of has been in to in breast cancer In the in we in the transfected cells that functionally of to a the cellular and of 21NT cells. in with a of tumor and of breast cancer cells of HAS2. be to in and in the of cells in the of the that in a the of in that a in the of the of the of cells how is to of to be in breast cancer cells constitutively the tumor and and the the in of to with with a to has a in tumor and tumor cells with the and and a and that behaviors. a that to the of Osteopontin (OPN) hyaluronan hyaluronan is that has been implicated in the progression and of breast OPN has been to with and in with breast in with breast cancer of the OPN functionally to OPN is to to and of the OPN-induced has been to cellular functions and OPN has been in to to the of a limited number been genes that contribute to OPN-induced microarray to the between 21NT control and breast cancer cells We genes OPN the of and genes the and we hyaluronan synthase 2 (HAS2) a gene highly up-regulated is a of of and is in the of and has been with progression of a of tumor and tumor progression is has been to be to to to with and to and is is of of the gene and is the of of of and the of of that contribute to tumor progression and metastasis. in cells in cancer cells to tumor in In of the of cells in of in cancer cells to to cells, of in breast cancer cells and tumor In this study, we and in cells constitutively OPN behaviors. we show that of OPN in a to and to and to cells. We show that of in cells in and of the of a relationship between OPN and in the of breast and in cells the 21NT with a a OPN of OPN the 21NT cells in in OPN and to transfected cells to the highly is to of cells of the of OPN in the control cells of the of OPN a of of cells with the to a and in with of the cells in a of and OPN and to the the analysis, and of to a of in a and and of gene the with and OPN and and and and and and to a of in and further in to the to the with the of the in a of and of of of the and and OPN and of and and of of the in in with gene of a and the of the the is to be the the of the and of the a the of the and to a of a in to in the with gene of of the the of the and of in gene the of the gene of to the the of the to the control the cells in in and to and the cells in the of in and of in with to and to cells a with the the the of cells and the and of the to of of of of of in in a number cells in in and to to cells with to and the to and and in a of the examined in to the and the of comparing the of to a of and to in with 2 of a of with the and to in a cells and to a of of a of with the and cells, the and to in a of to cells to with the of a of of cells with and in with a of and to the of the the cells in and with the between the with the of the with control and cells in in and to cells to the and to to cells in in a in cells in and to a of cells with the of with the of the with and of tumor cells and to cells with of cells in of and and in a and of the with of and control a of of the the the of the the and in the 21NT cells transfected with in to the cells to in and to with and and to transfected of in the of OPN and and and with in and of the cells in the of a cells and number a of and in cells the 21NT with a a OPN of OPN the 21NT cells in in OPN and to transfected cells to the highly is to of cells of the of OPN in the control cells of the of OPN a of of cells with the to a and in with of the cells in a of and OPN and to the the analysis, and of to a of in a and and of gene the with and OPN and and and and and and to a of in and further in to the to the with the of the in a of and of of of the and and OPN and of and and of of the in in with gene of a and the of the the is to be the the of the and of the a the of the and to a of a in to in the with gene of of the the of the and of in gene the of the gene of to the the of the to the control the cells in in and to and the cells in the of in and of in with to and to cells a with the the the of cells and the and of the to of of of of of in in a number cells in in and to to cells with to and the to and and in a of the examined in to the and the of comparing the of to a of and to in cells. with 2 of a of with the and to in a cells and to a of of a of with the and cells, the and to in a of to cells to with the of a of of cells with and in with a of and to the of the the cells in and with the between the with the of the with control and cells in in and to cells to the and to to cells in in a in cells in and to a of cells with the of with the of the with and of tumor cells and to cells with of cells in of and and in a and of the with of and control a of of the the the of the the and in the 21NT cells transfected with in to the cells to in and to with and and to transfected of in the of OPN and and and with in and of the cells in the of a cells and number a of in microarray 21NT control 21NT cells to genes OPN genes up-regulated OPN the gene we is of of the gene we to the of to the of in the 21NT cells. that is the highly up-regulated in the 21NT cells, with in to control cells is with microarray revealed a in in between to and of that with we a to the of secreted the 21NT 21NT cells with of of has been to in we a of to the and the 21NT cells. 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In this the cells with a of the and of the a a We in the 21NT cells, with a in with that that of we the cells with to the of the 21NT cells, and that cells secreted a of secreted and in the cells, further in cells to of 21NT is a of of cells. that of and of tumor cells in that the of in the 21NT cells the of cells in this we 21NT control and cells in and to In with of we that the cells and with control transfected cells, to in and the of the 21NT cells we 21NT cells in in the of of to with with the of of 21NT cells with in and of of 21NT to has been to the of breast and cancer cells to a in to the We the of 21NT control and cells to to and that 21NT cells OPN with control cells this is and cells with and to to with of 21NT cells to control cells in to a in this cellular of in the of of in the cells, we transfected the 21NT and revealed a in in the cells, in the control the cells that the in the cells to a of we examined OPN and in in the cells a in of OPN in the in and of of secreted we revealed of between the 21NT OPN-overexpressing transfected with control and the cells 21NT OPN-overexpressing we examined in of the of the with with in between control and in secreted and the in with the of in cells. of in in of the transfected examined a the 21NT OPN-overexpressing cells and transfected control cells the transfected cells of of 21NT OPN-overexpressing the in functionally we the of the cells in of in the cells in a in the of cells in with and control is a secreted phosphoprotein that has been to the progression of the OPN functions to been In this study, we that of OPN in the 21NT breast cancer in and of in cells to and to of in 21NT OPN-overexpressing cells led to a in and and a in in and in of and a OPN in breast of a of has been to a in the and of tumor breast and has been to contribute to and of and cells and to the of and breast cancer cells that cells OPN is in with in with of breast cancer cells OPN to to is a to the a of OPN in to the of and OPN has been of a gene is of OPN in breast cancer cells has been to in the that of OPN-overexpressing cells is of a that is with the of in tumor a of and has been to of and breast cancer cells to and in this has been to be in is that the in and 21NT OPN-overexpressing cells the and of the OPN a breast cancer cells OPN and to the of of a in the of breast cancer cells to in this is of the cells to the of control cells, that OPN be in the 21NT tumor to tumor show that cells OPN to in with and that of this of tumor cells to in has been to the of the OPN is to the of breast tumor cells and to of and OPN to in that of OPN in and in of has been to the of cancer to been to the to and the in the and of breast cancer cells constitutively OPN further a in the of in to and to OPN and the of in cells constitutively we a to show that the of in a in led to a in and the to the the in has been and in in cancer cells a in with the of in is to in of has been in to in breast cancer In the in we in the transfected cells that functionally of to a the cellular and of 21NT cells. in with a of tumor and of breast cancer cells of HAS2. be to in and in the of cells in the of the that in a the of in that a in the of the of the of cells how is to of to be in breast cancer cells constitutively the tumor and and the the in of to with with a to OPN is a secreted phosphoprotein that has been to the progression of the OPN functions to been In this study, we that of OPN in the 21NT breast cancer in and of in cells to and to of in 21NT OPN-overexpressing cells led to a in and and a in in and in of and a OPN in breast of a of has been to a in the and of tumor breast and has been to contribute to and of and cells and to the of and breast cancer cells that cells OPN is in with in with of breast cancer cells OPN to to is a to the a of OPN in to the of and OPN has been of a gene is of OPN in breast cancer cells has been to in the that of OPN-overexpressing cells is of a that is with the of in tumor a of and has been to of and breast cancer cells to and in this has been to be in is that the in and 21NT OPN-overexpressing cells the and of the OPN a breast cancer cells OPN and to the of of a in the of breast cancer cells to in this is of the cells to the of control cells, that OPN be in the 21NT tumor In to tumor show that cells OPN to in with and that of this of tumor cells to in has been to the of the OPN is to the of breast tumor cells and to of and OPN to in that of OPN in and in of has been to the of cancer to been to the to and the in the and of breast cancer cells constitutively OPN further a in the of in to and to OPN and the of in cells constitutively we a to show that the of in a in led to a in and the to the the in has been and in in cancer cells a in with the of in is to in of has been in to in breast cancer In the in we in the transfected cells that functionally of to a the cellular and of 21NT cells. in with a of tumor and of breast cancer cells of HAS2. be to in and in the of cells in the of the that in a the of in that a in the of the of the of cells how is to In of to be in breast cancer cells constitutively the tumor and and the the in of to with with a to We the and control and the We and of this and to with the

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