Good question.
Looking at a few things from a decade or so ago. In this excerpt it’s interesting that plexin-B1 back then was being studied in tumor angiogenesis, various cancers and that several class IV semaphorins back then were being classified as ‘immune semaphorins’.
“Intriguingly, semaphorins are also extensively involved in immune response regulation, qualifying some of them as "immune" semaphorins[5]. Recent studies have also focused on the pathological aspects, in particular on their links to several hallmarks of cancer such as tumor angiogenesis and invasiveness.”
…”Abstract
Sema4D, also known as CD100, is a protein belonging to class IV semaphorin. Its physiologic roles in the immune and nervous systems have been extensively explored. However, the roles of Sema4D have extended beyond these traditionally studied territories. Via interaction with its high affinity receptor Plexin-B1, Sema4D-Plexin-B1 involvement in tumor progression is strongly implied. Here, we critically review and delineate the Sema4D-Plexin-B1 interaction in many facets of tumor progression: tumor angiogenesis, regulation of tumor-associated macrophages and control of invasive growth. We correlate the in vitro and in vivo experimental data with the clinical study outcomes, and present a molecular mechanistic basis accounting for the intriguingly contradicting results from these recent studies.
Go to:
1. Introduction
Semaphorins are a large family of secreted, transmembrane or glycosylphosphatidylinositol-linked proteins containing a phylogenetically conserved extracellular "sema" domain. They are classified into eight classes, of which classes 3 to 7 contain vertebrate semaphorins[1]. Their major receptors have been identified as plexins. In contrast to semaphorins, plexins are transmembrane proteins containing a phylogenetically conserved intracellular "sex and plexins" domain. They are subdivided into plexin A to D subfamilies[2].
Since the discovery of semaphorins as axon guidance cues, semaphorin-plexin interactions have been traditionally best described in the nervous system. Recently their interactions in other systems have also been explored, notably in the cardiovascular development, following revelation of their regulatory roles in cellular motility[3,4]. Intriguingly, semaphorins are also extensively involved in immune response regulation, qualifying some of them as "immune" semaphorins[5]. Recent studies have also focused on the pathological aspects, in particular on their links to several hallmarks of cancer such as tumor angiogenesis and invasiveness. Indeed, these processes recapitulate the many semaphorin-plexin roles in physiologic development. Several recent reviews nicely summarized the accumulating evidence of semaphorin-plexin involvement in cancer progression [6-9]; however, the majority of the content referred to particularly secreted class 3 semaphorins. In this review, we focus on a transmembrane class 4 semaphorin, Sema4D and its receptor, plenxin-B1. We also present a molecular mechanistic basis to reconcile the conflicting results of these molecules in tumor progression from the recent studies.”
Not much from this publication from 2010 about CCR5 blockade. But links to CD72, VGEF etc. A quote or two as potential breadcrumbs for exploration.
“The mechanistic roles of Sema4D and Plexin-B1 in the tumor microenviroment such as tumor angiogenesis, regulation of tumor-associated macrophages as well as the invasiveness of the tumor itself are highlighted in the following discussion.”
“3. Sema4D acts as an angiogenic factor through its high affinity receptor Plexin-B1
Evidence demonstrating the proangiogenic properties of Sema4D has emerged from several in vitro and in vivo studies. Sema4D is able to induce cell migration and promote tubulogenesis in endothelial cells, mimicking pivotal events in angiogenesis. Notably, this angiogenic response elicited by Sema4D is comparable to that by other well-known angiogenic molecules such as VEGF-A, HGF, and bFGF and is independent of any up-regulation of these molecules.”
“Given its proangiogenic properties, the possible involvement of Sema4D in tumor angiogenesis was explored. Sema4D is indeed highly expressed in a wide range of human tumors such as prostate, colon, breast, oral, head and neck carcinomas as well as soft tissue sarcomas[30,31]. In one study employing head and neck squamous cell carcinoma cell lines with high expression of Sema4D, tumor growth and tumor angiogenesis in vivo were greatly impaired in the absence of Sema4D”
“4. Sema4D regulates monocytic lineage cells and tumor-associated macrophages in tumor microenvironment
Focusing on the effect of Sema4D on a monocytic lineage, an inhibitory effect on cell migration was demonstrated[16]. A recent study also showed that sequential engagement of CD72 and Plexin-B1 is crucial in this inhibitory effect during the maturation of monocytes into immature dendritic cells. Modulation of cytokine production towards either an anti-inflammatory or a pro-inflammatory cytokine profile seems to be dependent on Sema4D concentration”
“In tumor-associated macrophages, although the lack of Sema4D itself did not alter the differentiation and activation capabilities as well as the cytokine production profile, a significantly lower number of tumor-associated macrophages was observed in the tumor microenvironment[33]. However, the precise mechanism behind these findings awaits elucidation.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2955613/
Looking at a few things from a decade or so ago. In this excerpt it’s interesting that plexin-B1 back then was being studied in tumor angiogenesis, various cancers and that several class IV semaphorins back then were being classified as ‘immune semaphorins’.
“Intriguingly, semaphorins are also extensively involved in immune response regulation, qualifying some of them as "immune" semaphorins[5]. Recent studies have also focused on the pathological aspects, in particular on their links to several hallmarks of cancer such as tumor angiogenesis and invasiveness.”
…”Abstract
Sema4D, also known as CD100, is a protein belonging to class IV semaphorin. Its physiologic roles in the immune and nervous systems have been extensively explored. However, the roles of Sema4D have extended beyond these traditionally studied territories. Via interaction with its high affinity receptor Plexin-B1, Sema4D-Plexin-B1 involvement in tumor progression is strongly implied. Here, we critically review and delineate the Sema4D-Plexin-B1 interaction in many facets of tumor progression: tumor angiogenesis, regulation of tumor-associated macrophages and control of invasive growth. We correlate the in vitro and in vivo experimental data with the clinical study outcomes, and present a molecular mechanistic basis accounting for the intriguingly contradicting results from these recent studies.
Go to:
1. Introduction
Semaphorins are a large family of secreted, transmembrane or glycosylphosphatidylinositol-linked proteins containing a phylogenetically conserved extracellular "sema" domain. They are classified into eight classes, of which classes 3 to 7 contain vertebrate semaphorins[1]. Their major receptors have been identified as plexins. In contrast to semaphorins, plexins are transmembrane proteins containing a phylogenetically conserved intracellular "sex and plexins" domain. They are subdivided into plexin A to D subfamilies[2].
Since the discovery of semaphorins as axon guidance cues, semaphorin-plexin interactions have been traditionally best described in the nervous system. Recently their interactions in other systems have also been explored, notably in the cardiovascular development, following revelation of their regulatory roles in cellular motility[3,4]. Intriguingly, semaphorins are also extensively involved in immune response regulation, qualifying some of them as "immune" semaphorins[5]. Recent studies have also focused on the pathological aspects, in particular on their links to several hallmarks of cancer such as tumor angiogenesis and invasiveness. Indeed, these processes recapitulate the many semaphorin-plexin roles in physiologic development. Several recent reviews nicely summarized the accumulating evidence of semaphorin-plexin involvement in cancer progression [6-9]; however, the majority of the content referred to particularly secreted class 3 semaphorins. In this review, we focus on a transmembrane class 4 semaphorin, Sema4D and its receptor, plenxin-B1. We also present a molecular mechanistic basis to reconcile the conflicting results of these molecules in tumor progression from the recent studies.”
Not much from this publication from 2010 about CCR5 blockade. But links to CD72, VGEF etc. A quote or two as potential breadcrumbs for exploration.
“The mechanistic roles of Sema4D and Plexin-B1 in the tumor microenviroment such as tumor angiogenesis, regulation of tumor-associated macrophages as well as the invasiveness of the tumor itself are highlighted in the following discussion.”
“3. Sema4D acts as an angiogenic factor through its high affinity receptor Plexin-B1
Evidence demonstrating the proangiogenic properties of Sema4D has emerged from several in vitro and in vivo studies. Sema4D is able to induce cell migration and promote tubulogenesis in endothelial cells, mimicking pivotal events in angiogenesis. Notably, this angiogenic response elicited by Sema4D is comparable to that by other well-known angiogenic molecules such as VEGF-A, HGF, and bFGF and is independent of any up-regulation of these molecules.”
“Given its proangiogenic properties, the possible involvement of Sema4D in tumor angiogenesis was explored. Sema4D is indeed highly expressed in a wide range of human tumors such as prostate, colon, breast, oral, head and neck carcinomas as well as soft tissue sarcomas[30,31]. In one study employing head and neck squamous cell carcinoma cell lines with high expression of Sema4D, tumor growth and tumor angiogenesis in vivo were greatly impaired in the absence of Sema4D”
“4. Sema4D regulates monocytic lineage cells and tumor-associated macrophages in tumor microenvironment
Focusing on the effect of Sema4D on a monocytic lineage, an inhibitory effect on cell migration was demonstrated[16]. A recent study also showed that sequential engagement of CD72 and Plexin-B1 is crucial in this inhibitory effect during the maturation of monocytes into immature dendritic cells. Modulation of cytokine production towards either an anti-inflammatory or a pro-inflammatory cytokine profile seems to be dependent on Sema4D concentration”
“In tumor-associated macrophages, although the lack of Sema4D itself did not alter the differentiation and activation capabilities as well as the cytokine production profile, a significantly lower number of tumor-associated macrophages was observed in the tumor microenvironment[33]. However, the precise mechanism behind these findings awaits elucidation.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2955613/
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