Tumor-Induced Activation of Lymphatic Endothelial Cells via Vascular Endothelial Growth Factor Receptor-2 Is Critical for Prostate Cancer Lymphatic Metastasis

Zeng, Yiping; Opeskin, Kenneth; Goad, Jeremy; Williams, Elizabeth D.

doi:10.1158/0008-5472.can-06-1488

Cited by 64 publications

(68 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6). Although VEGFC stimulated LyECs to form tubes, as in previous studies (Podgrabinska et al 2002, Zeng et al 2006, IFNT promoted comparable levels of LyEC proliferation and capillary-like tube formation (Fig. 7).…”

Section: Discussionsupporting

confidence: 83%

Possible involvement of IFNT in lymphangiogenesis in the corpus luteum during the maternal recognition period in the cow

Nitta¹,

Shirasuna²,

Haneda³

et al. 2011

Reproduction

View full text Add to dashboard Cite

The corpus luteum (CL), which secretes large amounts of progesterone and is thus essential for establishing pregnancy, contains various types of immune cells that may play essential roles in CL function by generating immune responses. The lymphatic system is the second circulation system and is necessary for immune function, but the lymphatic system of the bovine CL has not been characterized in detail. We collected bovine CLs on days 12 and 16 of the estrous cycle (C12 and C16) and days 16 and 40 of early pregnancy (P16 and P40). Lymphatic endothelial hyaluronan receptor 1 (LYVE1) protein was detected in the CL by immunohistochemistry and western blotting and increased at P40 compared with C16. The mRNA expression levels of lymphangiogenic factors, such as vascular endothelial growth factor-C (VEGFC), VEGFD, and their common receptor VEGFR3, as well as the lymphatic endothelial cell (LyEC) marker podoplanin, increased in P16 and P40 CLs. Thus, it is suggested that the lymphatic system of the bovine CL reconstitutes during early pregnancy. Interferon tau (IFNT) from the conceptus in the uterus is a candidate for activating luteal lymphangiogenesis during the maternal recognition period (MRP). We found that treatment of LyECs isolated from internal iliac lymphatic vessels with IFNT stimulated LyEC proliferation and significantly increased mRNA expression of VEGFC and IFN-stimulated gene 15. Moreover, both IFNT and VEGFC induced LyECs to form capillary-like tubes in vitro.In conclusion, it is suggested that new lymphangiogenesis in the bovine CL begins during the MRP and that IFNT may mediate this novel phenomenon.

show abstract

Section: Discussionsupporting

confidence: 83%

Possible involvement of IFNT in lymphangiogenesis in the corpus luteum during the maternal recognition period in the cow

Nitta¹,

Shirasuna²,

Haneda³

et al. 2011

Reproduction

View full text Add to dashboard Cite

show abstract

“…To understand the mechanisms and to provide proof of metastatic spread observed in the mice injected with INHa-positive cells, we stained LNCaP and PC3 INHa and EV orthotopic tumours for LYVE-1, and human mitochondrial antibody to determine LVD and the degree of invasion of tumour cells into lymphatic vessels (lymphatic invasion) in the tissues. Consistent with our previous study (Zeng et al, 2006), the analysis of LNCaP tumours in the present study was complicated by the significantly larger size of the tumours compared to PC3 tumours.…”

Section: Lvd and Invasion Of Tumour Cells Into Lymphatics In Inha Ovesupporting

confidence: 89%

“…LNCaP (2 Â 10 6 ) or PC3 (5 Â 10 5 ) clones were injected orthotopically into the ventral lobe of the prostate gland (10 animals per clone) of male SCID mice as previously described (Zeng et al, 2006). After 7 -9 weeks, mice were killed and primary prostate tumours were removed and weighed.…”

Section: Analysis Of Clinical Materialsmentioning

confidence: 99%

“…Because VEGF-A and VEGF-C have been implicated in inducing/promoting metastasis to the lymph nodes in PCa (Karkkainen et al, 2002;Weis and Cheresh, 2005;Zeng et al, 2006), we went on to determine the expression of VEGF-A and VEGF-C proteins by ELISA (Table 3) to their EV clones, however there was no significant change in secreted VEGF-A levels.…”

Section: Factors Inducing Tumour Growth and Metastasis In Inha Over-ementioning

confidence: 99%

See 1 more Smart Citation

Elevated level of inhibin-α subunit is pro-tumourigenic and pro-metastatic and associated with extracapsular spread in advanced prostate cancer

et al. 2009

View full text Add to dashboard Cite

The biological function of inhibin-a subunit (INHa) in prostate cancer (PCa) is currently unclear. A recent study associated elevated levels of INHa in PCa patients with a higher risk of recurrence. This prompted us to use clinical specimens and functional studies to investigate the pro-tumourigenic and pro-metastatic function of INHa. We conducted a cross-sectional study to determine a link between INHa expression and a number of clinicopathological parameters including Gleason score, surgical margin, extracapsular spread, lymph node status and vascular endothelial growth factor receptor-3 expression, which are well-established prognostic factors of PCa. In addition, using two human PCa cell lines (LNCaP and PC3) representing androgen-dependent and -independent PCa respectively, we investigated the biological function of elevated levels of INHa in advanced cancer. (Wiater and Vale, 2003;Farnworth et al, 2007). This antagonistic effect of inhibin is amplified in the presence of the inhibin receptor, TGFb receptor III (TGFbRIII), also known as betaglycan.The first study that linked inhibin to reproductive cancers showed that serum inhibin increased in women with granulosa cell tumours of the ovary (Lappohn et al, 1989) and inhibin currently serves as a robust biomarker for this cancer. A direct biological function for inhibin in carcinogenesis was demonstrated by Matzuk et al (1992) when they created the inhibin-a subunit (INHa) knockout mouse. Both sexes developed gonadal sex-cord stromal tumours with high penetrance and developed tumours in their adrenal glands after castration, showing that INHa can act as a tumour suppressor. Subsequent mouse model studies revealed a complex network of interactions involving inhibin, activin and other modifiers in the development and progression of gonadal and adrenal tumours in INHa-deficient mice (reviewed in Risbridger et al, 2001). Although it is clear that total inhibin as a serum test has utility in the initial detection and prognosis of certain types of ovarian cancers, the biological function of inhibin in tumourigenesis is far from clear.We have observed both up-and down-regulation of INHa expression in prostate cancer (PCa) tissues dependent on the stage

show abstract

“…39 Theoretically, tumors developing in situ in the prostate may have immediate access to a more elaborate network of preexisting large lymphatics than tumors implanted in subcutaneous locations. Thus it is possible that while the former may achieve access to the lymphatic network by expressing lymphangiogenic growth factors that act to enlarge and dilate preexisting lymph vessels, 42 the latter may depend more on genuine stimulation of lymphangiogenesis, either in the tumor periphery or intratumorally, to establish contact with the lymphatic network and generate lymphatic metastasis.…”

Section: Discussionmentioning

confidence: 99%

Modulating metastasis by a lymphangiogenic switch in prostate cancer

Bråkenhielm

Burton

Johnson

et al. 2007

Intl Journal of Cancer

View full text Add to dashboard Cite

Prostate cancer dissemination is difficult to detect in the clinic, and few treatment options exist for patients with advanced-stage disease. Our aim was to investigate the role of tumor lymphangiogenesis during metastasis. Further, we implemented a noninvasive molecular imaging technique to facilitate the assessment of the metastatic process. The metastatic potentials of several human prostate cancer xenograft models, LAPC-4, LAPC-9, PC3 and CWR22Rv-1 were compared. The cells were labeled with luciferase, a bioluminescence imaging reporter gene, to enable optical imaging. After tumor implantation the animals were examined weekly during several months for the appearance of metastases. Metastatic lesions were confirmed by immunohistochemistry. Additionally, the angiogenic and lymphangiogenic profiles of the tumors were characterized. To confirm the role of lymphangiogenesis in mediating metastasis, the low-metastatic LAPC-9 tumor cells were engineered to overexpress VEGF-C, and the development of metastases was evaluated. Our results show CWR22Rv-1 and PC3 tumor cell lines to be more metastatic than LAPC-4, which in turn disseminates more readily than LAPC-9. The difference in metastatic potential correlated with the endogenous production levels of lymphangiogenic growth factor VEGF-C and the presence of tumor lymphatics. In agreement, induced overexpression of VEGF-C in LAPC-9 enhanced tumor lymphangiogenesis leading to the development of metastatic lesions. Taken together, our studies, based on a molecular imaging approach for semiquantitative detection of micrometastases, point to an important role of tumor lymphatics in the metastatic process of human prostate cancer. In particular, VEGF-C seems to play a key role in prostate cancer metastasis. ' 2007 Wiley-Liss, Inc.

show abstract

Tumor-Induced Activation of Lymphatic Endothelial Cells via Vascular Endothelial Growth Factor Receptor-2 Is Critical for Prostate Cancer Lymphatic Metastasis

Cited by 64 publications

References 40 publications

Possible involvement of IFNT in lymphangiogenesis in the corpus luteum during the maternal recognition period in the cow

Possible involvement of IFNT in lymphangiogenesis in the corpus luteum during the maternal recognition period in the cow

Elevated level of inhibin-α subunit is pro-tumourigenic and pro-metastatic and associated with extracapsular spread in advanced prostate cancer

Modulating metastasis by a lymphangiogenic switch in prostate cancer

Contact Info

Product

Resources

About