کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5890392 | 1568156 | 2014 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Paracrine interactions between LNCaP prostate cancer cells and bioengineered bone in 3D in vitro culture reflect molecular changes during bone metastasis
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کلمات کلیدی
ParacrineKrt8TEB3D culturesKLKTGFβ1HOBKallikreinIPAPSAIL-6PCA - PCAProstate specific antigen - آنتی ژن اختصاصی پروستاتAndrogen - آندروژنHuman osteoblast - استئوآلبوز انسانیinterleukin 6 - اینترلوکین 6transforming growth factor beta 1 - تبدیل فاکتور رشد بتا 1Ingenuity Pathway Analysis - تجزیه و تحلیل راه IngenuityProstate cancer - سرطان پروستاتcytokeratin 8 - سیتوکراتین 8Bone metastasis - متاستاز های استخوانpolyethylene glycol - پلی اتیلن گلیکولPEG - پلیاتیلن گلیکول Androgen Receptor - گیرنده آندروژنی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شناسی تکاملی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
As microenvironmental factors such as three-dimensionality and cell-matrix interactions are increasingly being acknowledged by cancer biologists, more complex 3D in vitro models are being developed to study tumorigenesis and cancer progression. To better understand the pathophysiology of bone metastasis, we have established and validated a 3D indirect co-culture model to investigate the paracrine interactions between prostate cancer (PCa) cells and human osteoblasts. Co-culture of the human PCa, LNCaP cells embedded within polyethylene glycol hydrogels with human osteoblasts in the form of a tissue engineered bone construct (TEB), resulted in reduced proliferation of LNCaP cells. LNCaP cells in both monoculture and co-culture were responsive to the androgen analog, R1881, as indicated by an increase in the expression (mRNA and/or protein induction) of androgen-regulated genes including prostate specific antigen and fatty acid synthase. Microarray gene expression analysis further revealed an up-regulation of bone markers and other genes associated with skeletal and vasculature development and a significant activation of transforming growth factor β1 downstream genes in LNCaP cells after co-culture with TEB. LNCaP cells co-cultured with TEB also unexpectedly showed similar changes in classical androgen-responsive genes under androgen-deprived conditions not seen in LNCaP monocultures. The molecular changes of LNCaP cells after co-culturing with TEBs suggest that osteoblasts exert a paracrine effect that may promote osteomimicry and modulate the expression of androgen-responsive genes in LNCaP cells. Taken together, we have presented a novel 3D in vitro model that allows the study of cellular and molecular changes occurring in PCa cells and osteoblasts that are relevant to metastatic colonization of bone. This unique in vitro model could also facilitate cancer biologists to dissect specific biological hypotheses via extensive genomic or proteomic assessments to further our understanding of the PCa-bone crosstalk.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bone - Volume 63, June 2014, Pages 121-131
Journal: Bone - Volume 63, June 2014, Pages 121-131
نویسندگان
Shirly Sieh, Anna V. Taubenberger, Melanie L. Lehman, Judith A. Clements, Colleen C. Nelson, Dietmar W. Hutmacher,