<i>Tumor endothelial marker 1</i>
            (
            <i>Tem1</i>
            ) functions in the growth and progression of abdominal tumors

Nanda, Akash; Karim, Baktiar O.; Peng, Zhongsheng; Liu, Guosheng; Qiu, Weiping; Gan, Christine; Vogelstein, Bert; Croix, Brad St.; Kinzler, Kenneth W.; Huso, David L.

doi:10.1073/pnas.0511306103

Cited by 129 publications

(172 citation statements)

References 31 publications

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“…This results in an increase in CD248 expression, via hypoxia inducible factor-2a [9], which in turn is required for full expansion of pLN. This is analogous to the previous studies where lack of CD248 inhibited full expansion of abdominal tumours [8]. …”

supporting

confidence: 90%

The pericyte and stromal cell marker CD248 (endosialin) is required for efficient lymph node expansion

et al. 2010

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CD248 is a cell surface receptor that specifically identifies fibroblasts and pericytes during development and in association with cancer and inflammation. However, its function is poorly defined and its role in lymphoid organs not studied. Here, we used (4-hydroxy-3-nitrophenyl)acetyl chicken c-globulin immunisation and mice lacking CD248 to study whether CD248 modulates popliteal LN (pLN) expansion and subsequent immune responses. We have found that CD248 is required for complete pLN expansion but not for co-ordination of B and T cell compartmentalisation or antibody production following (4-hydroxy-3-nitrophenyl)acetyl chicken c-globulin immunisation. In vitro, we show that CD248 expression in human MG63 stromal cells and mouse embryonic fibroblasts leads to a pro-proliferative and pro-migratory phenotype. This correlates with a proliferating CD248 1 population observed in vivo during pLN expansion. Taken together, these data highlight a role for CD248 in secondary lymphoid organ remodelling during adaptive immune responses.Key words: CD248 . Endosialin . Fibroblast . Lymphoid tissue . Stromal cells IntroductionDuring an immune response, secondary lymphoid organs (SLO) expand significantly. However, mechanisms that regulate this have been relatively understudied with leucocyte accumulation rather than stromal cell expansion being the focus. Logic dictates that there has to be co-ordinated expansion of tissue structure to accommodate the rapidly expanding leucocyte populations. This expansion includes not only an intricate network of fibroblasts that provide an important structural scaffold but also the formation of new blood and lymph vessels to oxygenate and allow transport of lymphocytes into and out of the organ [1].CD248/endosialin is a relatively new marker for a subset of stromal cells in developing tissues. It is a member of an emerging transmembrane protein family implicated in tissue remodelling and repair, which includes CD141 and CD93 [2,3] 1884expressed on fibroblasts and pericytes during development and in tumour-associated stroma [4][5][6][7]. An important role for CD248 within tumour stroma has been highlighted in CD248-deficient mice; abdominal tumours implanted into mice lacking CD248 demonstrated reduced growth, invasion and metastasis [8]. This, coupled with the finding that CD248 expression is regulated by hypoxia inducible factor-2a [9], suggests that CD248 may provide an important link between hypoxia and tissue remodelling allowing synchronisation of these processes.We have previously proposed a role for CD248 in development and infection-dependent activation of SLO stroma [10]. Whether CD248 is required for tissue remodelling was not explored nor was its function. Therefore, to more fully understand the requirements for CD248 during remodelling, we compared the degree of popliteal LN (pLN) expansion in WT and CD248 KO mice following immunisation with (4-hydroxy-3-nitrophenyl)acetyl chicken g-globulin (NP-CGG). The ability of CD248 to regulate cell migration and proliferation in vitro w...

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supporting

confidence: 90%

The pericyte and stromal cell marker CD248 (endosialin) is required for efficient lymph node expansion

et al. 2010

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“…Similarly, in situ hybridization analysis has demonstrated an upregulation of endosialin mRNAs in the tumor vasculature but again this method cannot distinguish between an endothelial and perivascular localization of the signal. 5,14,17 As endosialin is also expressed in the developing vasculature, different laboratories have performed double labeling of cryosections both from tumors and developing tissues. However, disparate results have been obtained in that it has been reported that endosialin is only expressed on the endothelial cells, 12 only on the pericytes 9,13,18 and on both.…”

Section: Discussionmentioning

confidence: 99%

“…The significance of these findings is twofold. First, mice with a homozygous deletion in endosialin (Cd248) show impaired growth, invasion and vascularization of implanted abdominal tumors, 17 suggesting that endosialin expression on pericytes has an important functional role in the tumor vasculature. Second, there is increasing evidence that antiangiogenic therapies targeting both endothelial cells and pericytes are more effective than single-agent therapies.…”

Section: Discussionmentioning

confidence: 99%

Endosialin (CD248) is a marker of tumor-associated pericytes in high-grade glioma

et al. 2008

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Gliomas are the most frequent primary tumors of the central nervous system in adults. The most prevalent and aggressive subclass of these is glioblastoma multiforme, which is characterized by massive neovascularization. Endosialin (CD248) has generated interest as a target for antiangiogenic therapy following reports that its expression is upregulated on angiogenic endothelial cells. We demonstrate here that endosialin is not expressed in normal human adult brain but is strongly upregulated in the angiogenic vasculature of all high-grade glioma specimens examined. However, by taking advantage of a technique which allows for multiple fluorescent labeling of formalin-fixed paraffin-embedded archival sections, we demonstrate unambiguously that endosialin is not expressed by the glioma endothelial cells but on closely associated perivascular cells. With increasing awareness that targeting pericytes is an attractive adjunct in antiangiogenic therapy, this finding has important implications for understanding the molecular mechanisms regulating angiogenesis in these highly vascularized tumors.

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“…Although not expressed by endothelium (MacFadyen et al, 2005), TEM1/endosialin mediates tumor, but not developmental angiogenesis. Thus, orthotopically implanted colon tumors grow slower in the TEM1/endosialin À/À mouse, whereas developmental angiogenesis is normal (Nanda et al, 2006). Endothelial-specific expression of CLE-C14A and functional studies now confirm a role for this type 14 C-type lectin family member in vascular biology.…”

Section: Clec14a Is a Novel Tumor Endothelial Markermentioning

confidence: 90%

Identification and angiogenic role of the novel tumor endothelial marker CLEC14A

et al. 2011

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Tumor endothelial marker 1 ( Tem1 ) functions in the growth and progression of abdominal tumors

Cited by 129 publications

References 31 publications

The pericyte and stromal cell marker CD248 (endosialin) is required for efficient lymph node expansion

The pericyte and stromal cell marker CD248 (endosialin) is required for efficient lymph node expansion

Endosialin (CD248) is a marker of tumor-associated pericytes in high-grade glioma

Identification and angiogenic role of the novel tumor endothelial marker CLEC14A

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