THE ROLE OF PREGNANCY IN PROMOTING NON-HODGKIN LYMPHOMA GROWTH AND AGGRESSIVENESS
(Abstract release date: 05/19/16)
EHA Library. Katz T. 06/09/16; 132935; E1386
Prof. Dr. Tami Katz
Contributions
Contributions
Abstract
Abstract: E1386
Type: Eposter Presentation
Background
Lymphoma is the most common hematological cancer reported during pregnancy. Recent data suggest that unlike lymphoma occurring outside of pregnancy, pregnancy-associated non-Hodgkin lymphoma is characterized by an excessive involvement of reproductive organs, advanced disease stage at diagnosis and an aggressive course, potentially leading to a high death rate of mothers. However, the mechanisms facilitating this clinical phenomenon are not fully defined.
Aims
The current study aimed to explore the hypothesis that pregnancy-induced hormonal milieu could be an important mediator in the interaction between lymphoma cells and their associated microenvironment, which may potentially contribute to the growth and progress of lymphoma developing during pregnancy.
Methods
BALB/c pregnant and non-pregnant mice were subcutaneously (s.c.) inoculated with murine B cell lymphoma cells (A20). Primary tumor growth was measured biweekly in both groups. Several human lymphoma cell lines (Ramos, Raji and Bl2) and the human lymph node (LN) stromal cell line (HK) were assessed using flow cytometry, Western blot and qPCR analysis, for the expression of estrogen and progesterone receptors (ER α&β and PR, respectively). The direct effect of estradiol (E2) or progesterone on lymphoma cell proliferation was analyzed by trypan blue exclusion. The effect of E2 on the expression of growth factors VEGF-C and VEGF-D and their receptor VEGFR3 in lymphoma and stromal cells was analyzed by qPCR. Similarly, the expression of metalloproteinases MMP-2 and MMP-9 was evaluated.
Results
Pregnant mice showed a significantly accelerated tumor growth, as demonstrated by its increased volume and weight, following lymphoma cell inoculation compared to non-pregnant mice (Fig. 1). All the three lymphoma cell lines, as well as LN stromal cells were found to express ER α&β, but not PR. The Ramos lymphoma cell line treated with E2 demonstrated an increased proliferation rate. This effect was found to be mediated by ERα. In contrast, progesterone appeared to have no effect on lymphoma cell proliferation or viability. Furthermore, E2 induced the expression of VEGF-C and VEGF-D mRNA in lymphoma and LN stromal cells. Notably, the expression of their receptor VEGFR-3 was elevated in lymphoma cells. Likewise, E2 treatment resulted in increased expression of MMP-2 and MMP-9 mRNA in lymphoma and LN stromal cells, respectively.
Conclusion
The results of the current study have demonstrated for the first time that pregnancy significantly enhances lymphoma growth in vivo. This finding could be partially explained by a direct impact of pregnancy-induced estrogen on lymphoma cell proliferation through its effect on the expression of growth factors and metalloproteinases on lymphoma and LN stromal cells. These potential mechanisms need to be be further explored and validated.
Session topic: E-poster
Keyword(s): Non-Hodgkin's lymphoma, Pregnancy
Type: Eposter Presentation
Background
Lymphoma is the most common hematological cancer reported during pregnancy. Recent data suggest that unlike lymphoma occurring outside of pregnancy, pregnancy-associated non-Hodgkin lymphoma is characterized by an excessive involvement of reproductive organs, advanced disease stage at diagnosis and an aggressive course, potentially leading to a high death rate of mothers. However, the mechanisms facilitating this clinical phenomenon are not fully defined.
Aims
The current study aimed to explore the hypothesis that pregnancy-induced hormonal milieu could be an important mediator in the interaction between lymphoma cells and their associated microenvironment, which may potentially contribute to the growth and progress of lymphoma developing during pregnancy.
Methods
BALB/c pregnant and non-pregnant mice were subcutaneously (s.c.) inoculated with murine B cell lymphoma cells (A20). Primary tumor growth was measured biweekly in both groups. Several human lymphoma cell lines (Ramos, Raji and Bl2) and the human lymph node (LN) stromal cell line (HK) were assessed using flow cytometry, Western blot and qPCR analysis, for the expression of estrogen and progesterone receptors (ER α&β and PR, respectively). The direct effect of estradiol (E2) or progesterone on lymphoma cell proliferation was analyzed by trypan blue exclusion. The effect of E2 on the expression of growth factors VEGF-C and VEGF-D and their receptor VEGFR3 in lymphoma and stromal cells was analyzed by qPCR. Similarly, the expression of metalloproteinases MMP-2 and MMP-9 was evaluated.
Results
Pregnant mice showed a significantly accelerated tumor growth, as demonstrated by its increased volume and weight, following lymphoma cell inoculation compared to non-pregnant mice (Fig. 1). All the three lymphoma cell lines, as well as LN stromal cells were found to express ER α&β, but not PR. The Ramos lymphoma cell line treated with E2 demonstrated an increased proliferation rate. This effect was found to be mediated by ERα. In contrast, progesterone appeared to have no effect on lymphoma cell proliferation or viability. Furthermore, E2 induced the expression of VEGF-C and VEGF-D mRNA in lymphoma and LN stromal cells. Notably, the expression of their receptor VEGFR-3 was elevated in lymphoma cells. Likewise, E2 treatment resulted in increased expression of MMP-2 and MMP-9 mRNA in lymphoma and LN stromal cells, respectively.
Conclusion
The results of the current study have demonstrated for the first time that pregnancy significantly enhances lymphoma growth in vivo. This finding could be partially explained by a direct impact of pregnancy-induced estrogen on lymphoma cell proliferation through its effect on the expression of growth factors and metalloproteinases on lymphoma and LN stromal cells. These potential mechanisms need to be be further explored and validated.
Session topic: E-poster
Keyword(s): Non-Hodgkin's lymphoma, Pregnancy
Abstract: E1386
Type: Eposter Presentation
Background
Lymphoma is the most common hematological cancer reported during pregnancy. Recent data suggest that unlike lymphoma occurring outside of pregnancy, pregnancy-associated non-Hodgkin lymphoma is characterized by an excessive involvement of reproductive organs, advanced disease stage at diagnosis and an aggressive course, potentially leading to a high death rate of mothers. However, the mechanisms facilitating this clinical phenomenon are not fully defined.
Aims
The current study aimed to explore the hypothesis that pregnancy-induced hormonal milieu could be an important mediator in the interaction between lymphoma cells and their associated microenvironment, which may potentially contribute to the growth and progress of lymphoma developing during pregnancy.
Methods
BALB/c pregnant and non-pregnant mice were subcutaneously (s.c.) inoculated with murine B cell lymphoma cells (A20). Primary tumor growth was measured biweekly in both groups. Several human lymphoma cell lines (Ramos, Raji and Bl2) and the human lymph node (LN) stromal cell line (HK) were assessed using flow cytometry, Western blot and qPCR analysis, for the expression of estrogen and progesterone receptors (ER α&β and PR, respectively). The direct effect of estradiol (E2) or progesterone on lymphoma cell proliferation was analyzed by trypan blue exclusion. The effect of E2 on the expression of growth factors VEGF-C and VEGF-D and their receptor VEGFR3 in lymphoma and stromal cells was analyzed by qPCR. Similarly, the expression of metalloproteinases MMP-2 and MMP-9 was evaluated.
Results
Pregnant mice showed a significantly accelerated tumor growth, as demonstrated by its increased volume and weight, following lymphoma cell inoculation compared to non-pregnant mice (Fig. 1). All the three lymphoma cell lines, as well as LN stromal cells were found to express ER α&β, but not PR. The Ramos lymphoma cell line treated with E2 demonstrated an increased proliferation rate. This effect was found to be mediated by ERα. In contrast, progesterone appeared to have no effect on lymphoma cell proliferation or viability. Furthermore, E2 induced the expression of VEGF-C and VEGF-D mRNA in lymphoma and LN stromal cells. Notably, the expression of their receptor VEGFR-3 was elevated in lymphoma cells. Likewise, E2 treatment resulted in increased expression of MMP-2 and MMP-9 mRNA in lymphoma and LN stromal cells, respectively.
Conclusion
The results of the current study have demonstrated for the first time that pregnancy significantly enhances lymphoma growth in vivo. This finding could be partially explained by a direct impact of pregnancy-induced estrogen on lymphoma cell proliferation through its effect on the expression of growth factors and metalloproteinases on lymphoma and LN stromal cells. These potential mechanisms need to be be further explored and validated.
Session topic: E-poster
Keyword(s): Non-Hodgkin's lymphoma, Pregnancy
Type: Eposter Presentation
Background
Lymphoma is the most common hematological cancer reported during pregnancy. Recent data suggest that unlike lymphoma occurring outside of pregnancy, pregnancy-associated non-Hodgkin lymphoma is characterized by an excessive involvement of reproductive organs, advanced disease stage at diagnosis and an aggressive course, potentially leading to a high death rate of mothers. However, the mechanisms facilitating this clinical phenomenon are not fully defined.
Aims
The current study aimed to explore the hypothesis that pregnancy-induced hormonal milieu could be an important mediator in the interaction between lymphoma cells and their associated microenvironment, which may potentially contribute to the growth and progress of lymphoma developing during pregnancy.
Methods
BALB/c pregnant and non-pregnant mice were subcutaneously (s.c.) inoculated with murine B cell lymphoma cells (A20). Primary tumor growth was measured biweekly in both groups. Several human lymphoma cell lines (Ramos, Raji and Bl2) and the human lymph node (LN) stromal cell line (HK) were assessed using flow cytometry, Western blot and qPCR analysis, for the expression of estrogen and progesterone receptors (ER α&β and PR, respectively). The direct effect of estradiol (E2) or progesterone on lymphoma cell proliferation was analyzed by trypan blue exclusion. The effect of E2 on the expression of growth factors VEGF-C and VEGF-D and their receptor VEGFR3 in lymphoma and stromal cells was analyzed by qPCR. Similarly, the expression of metalloproteinases MMP-2 and MMP-9 was evaluated.
Results
Pregnant mice showed a significantly accelerated tumor growth, as demonstrated by its increased volume and weight, following lymphoma cell inoculation compared to non-pregnant mice (Fig. 1). All the three lymphoma cell lines, as well as LN stromal cells were found to express ER α&β, but not PR. The Ramos lymphoma cell line treated with E2 demonstrated an increased proliferation rate. This effect was found to be mediated by ERα. In contrast, progesterone appeared to have no effect on lymphoma cell proliferation or viability. Furthermore, E2 induced the expression of VEGF-C and VEGF-D mRNA in lymphoma and LN stromal cells. Notably, the expression of their receptor VEGFR-3 was elevated in lymphoma cells. Likewise, E2 treatment resulted in increased expression of MMP-2 and MMP-9 mRNA in lymphoma and LN stromal cells, respectively.
Conclusion
The results of the current study have demonstrated for the first time that pregnancy significantly enhances lymphoma growth in vivo. This finding could be partially explained by a direct impact of pregnancy-induced estrogen on lymphoma cell proliferation through its effect on the expression of growth factors and metalloproteinases on lymphoma and LN stromal cells. These potential mechanisms need to be be further explored and validated.
Session topic: E-poster
Keyword(s): Non-Hodgkin's lymphoma, Pregnancy
{{ help_message }}
{{filter}}