Magnus Edlund - Academia.edu (original) (raw)

Papers by Magnus Edlund

Copyright information:Taken from "Met-Independent Hepatocyte Growth Facto... more Copyright information:Taken from "Met-Independent Hepatocyte Growth Factor-mediated regulation of cell adhesion in human prostate cancer cells"BMC Cancer 2006;6():197-197.Published online 25 Jul 2006PMCID:PMC1559714. (A) Cell spreading behaviors on laminin substrata for PC3 and C4-2 cells exposed to variable concentrations of purified HGF. Because the cells differ in untreated attachment speeds, experiments were terminated at 30 minutes for PC3 cells and 90 minutes for C4-2 cells. At these times, with high concentrations of HGF, filopodia and lamelipodia were visible in approximately 90% of PC3 cells and 65% of C4-2 cells. Both cell lines show a concentration-dependent increase in cell spreading. (B) HGF induction of C4-2 cell spreading is matrix-dependent, with spreading increasing only on laminin-1 matrix (laminin, Fibronectin, Collagen I, and Vitronectin are LM, FN, CollI and VN, respectively). Experimental cell spreading is shown as a percentage of control, untreated cells. Statistically significant differences from the control in each group were below P =< 0.05 (*). For each data point n = 6 or more.

Current Biology, May 15, 2000

Background: Cell migration has been studied extensively by manipulating and observing cells bathe... more Background: Cell migration has been studied extensively by manipulating and observing cells bathed in putative chemotactic or chemokinetic agents on planar substrates. This environment differs from that in vivo and, consequently, the cells can behave abnormally. Embryo slices provide an optically accessible system for studying cellular navigation pathways during development. We extended this system to observe the migration of muscle precursors from the somite into the forelimb, their cellular morphology, and the localization ...

Advances in cancer research, 2004

The hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, the Met protein tyrosine k... more The hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, the Met protein tyrosine kinase, form a classic ligand-receptor system for epithelial-mesenchymal communications in the normal and cancerous prostate. This review illustrates the expression and activities of HGF/SF and Met during prostate development, homeostasis, and carcinogenesis. The participation of HGF/SF in the morphogenetic program of rodent prostate development, the role of Met in normal human prostate epithelium, and underlying mechanisms of deregulated Met expression in localized and metastatic prostate cancer are discussed. On the basis of the commonly observed overexpression of Met in metastatic prostate cancer, HGF/SF-Met-targeted imaging and therapeutic agents can now be applied toward diagnosis and treatment.

Clinical Genitourinary Cancer, 2006

Cancer is not a single-cell disease, and its existence and behavior are constantly modulated by t... more Cancer is not a single-cell disease, and its existence and behavior are constantly modulated by the host. Cancer gene expression and genetics are also highly dynamic and are regulated epigenetically by the host through gene-environment interaction. In this article, we describe the molecular pathways leading to an unusual property of cancer cells: the ability to mimic the host microenvironment and, in particular, the characteristics of osteomimicry and vasculogenic mimicry, which are likely to be regulated by soluble and insoluble factors in the tumor-adjacent microenvironment. We also discuss the importance of host inflammatory and stem cells that contribute to the growth and survival of cancer cells. By understanding the salient features of cancer-host interaction, novel therapeutics might be developed to target the cancer and its host in the treatment of lethal prostate cancer metastases.

Copyright information:Taken from "Met-Independent Hepatocyte Growth Facto... more Copyright information:Taken from "Met-Independent Hepatocyte Growth Factor-mediated regulation of cell adhesion in human prostate cancer cells"BMC Cancer 2006;6():197-197.Published online 25 Jul 2006PMCID:PMC1559714. (A) Met was precipitated in the PC3 cell line, while (B) in the C4-2 cell line two bands were precipitated using HGF coated beads but not with BSA control beads. The lower major band is HGF itself; the upper 100 kDa band was purified and sequenced. Western-blot analyses (C) and sequencing of the upper band confirmed it to be nucleolin (see table 2). (D) The importance of nucleolin to HGF-stimulated spreading on laminin substrata was apparent when antibodies to nucleolin reduced the effect of HGF (E). The cell spreading behaviors were quantified and presented as the mean of triplicate experiments. Statistically significant differences from the control were at P =< 0.005 (*).

Copyright information:Taken from "Met-Independent Hepatocyte Growth Facto... more Copyright information:Taken from "Met-Independent Hepatocyte Growth Factor-mediated regulation of cell adhesion in human prostate cancer cells"BMC Cancer 2006;6():197-197.Published online 25 Jul 2006PMCID:PMC1559714. (A) All cell lines, except LNCaP, increased cell spreading on laminin, following exposure to the SCM. (B) C4-2 cell attachment to laminin, following treatment with SCM or purified HGF. Cells were allowed to attach for 90 min., at which point ~25% of untreated C4-2 cells showed membrane protrusions. Induction of cell spreading, as seen for both SCM and purified HGF, is reversible by addition of anti-HGF antibody. Conditioned media from three primary stromal cell lines gave similar results (data not shown). Experimental cell spreading is shown as a percentage of control, untreated cells. Statistically significant differences from the control in each group were below P =< 0.05 (*). For each data point n = 6 or more.

International Journal of Cancer, 2004

At autopsy &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;a... more At autopsy &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or=80% of prostate cancers have established macrometastases in marrow containing bone. The mechanism(s) to explain this remarkable level of bone involvement remain to be elucidated. We examined the adhesive and invasive behavior of prostate cancer cells to osteoblastic and human bone marrow endothelial cells (HBME-1) in an attempt to explain the tropism of prostate cells for bone. We found an inverse relationship between adhesion and prostate cell tumorigenicity and metastatic potential. Relative cell adhesion of P69 between cell lines was 1.74-fold (95% confidence interval [CI] = 1.15-2.64) and 1.58-fold (95% CI = 0.94-2.68) greater at 1 hr and 2 hr, respectively, than LNCaP that was essentially equivalent to C4-2 cells when using an osteoblastic cell line, D1 as the substrate. Similar results were acquired when HBME-1 were used as substratum. There was a marked increase in adhesion of the poorly tumorigenic cell line P69 as compared to the cancer cells to HBME-1. P69 adhesion was 2.78-fold (95% CI = 1.87-4.84) and 2.0-fold (95% CI = 1.43-2.80) greater at 1 hr and 2 hr, respectively when compared to LNCaP or C4-2 cells. D1 cells, a bone homing osteoblastic precursor, behaved contrary to the metastatic, bone-colonizing C4-2 cell line and bound best to other bone cells but not as well as a non-homing fetal bone marrow-derived cell line, D2. Invasion of prostate cancer cells through HBME-1 lawns was examined at 8 hr and 16 hr. In contrast to the adhesion studies, the invasion of the more aggressive C4-2 cells was 3.46-fold (95% CI = 1.18-10.17) and 2.65-fold (95% CI = 1.26-5.56) greater at 8 hr and 16 hr, respectively than LNCaP cells. Similarly, LNCaP cell invasion was 1.73-fold (95% CI = 0.69-4.37) and 2.35-fold (95% CI = 1.41-3.93) greater at 8 hr and 16 hr, respectively than P69 cells at the invasion of HBME-1 monolayers. At 8 hr, C4-2 cells had 6.0-fold (95% CI = 2.63,13.65) higher invasive potential than P69 cells. Phage display biopanning of LNCaP cells versus C4-2 cells in vitro using 4 separate techniques repeatedly identified the same peptide in support of minimal cell surface changes associated with the ability of C4-2 cells to metastasize to bone. As integrins are vital to cell adhesion and migration, we examined the integrin subunit expression in the prostate cell lines. The expression of integrin subunits is much higher in the nontumorigenic cell line, P69, whereas the differences in integrin expression between LNCaP and C4-2 are negligible. Only alpha(2) and beta(5) integrin subunits increase from LNCaP to C4-2. Given that C4-2 cells spontaneously metastasize to bone in vivo and LNCaP cells do not, these studies imply that the ability of a metastatic prostate cancer cell to colonize the bone is not completely dependent upon the ability of the cancer cell to adhere to either osteoblastic cells or to the bone marrow endothelial cell lining. Therefore, the initial interaction between the bone endothelium or stroma and prostate cells is not accurately referred to as a tropic or homing response. The invasion assay results indicate that the invasive potential of the cell more accurately reflects the bone colonizing potential of a prostate cancer cell. It is likely that bidirectional paracrine interactions, subsequent to marrow adhesion, between prostate cancer cells and the bone microenvironment are what determine the successful colonization of the bone by prostate cancer cells. Further, functional changes in surface proteins that are involved in invasion are likely to occur without major changes in levels of cell surface protein expression. Functional integrin association, substratum usage and outside in signaling are more likely to predict metastatic behavior.

Journal of Biological Chemistry, 1996

Molecular Biology of the Cell, 2004

To study the dynamics of stress fiber components in cultured fibroblasts, we expressed α-actinin ... more To study the dynamics of stress fiber components in cultured fibroblasts, we expressed α-actinin and the myosin II regulatory myosin light chain (MLC) as fusion proteins with green fluorescent protein. Myosin activation was stimulated by treatment with calyculin A, a serine/threonine phosphatase inhibitor that elevates MLC phosphorylation, or with LPA, another agent that ultimately stimulates phosphorylation of MLC via a RhoA-mediated pathway. The resulting contraction caused stress fiber shortening and allowed observation of changes in the spacing of stress fiber components. We have observed that stress fibers, unlike muscle myofibrils, do not contract uniformly along their lengths. Although peripheral regions shortened, more central regions stretched. We detected higher levels of MLC and phosphorylated MLC in the peripheral region of stress fibers. Fluorescence recovery after photobleaching revealed more rapid exchange of myosin and α-actinin in the middle of stress fibers, compar...

Developmental Brain Research, 1994

C-CAM, a transmembrane glycoprotein belonging to the immunoglobulin superfamily, can mediate inte... more C-CAM, a transmembrane glycoprotein belonging to the immunoglobulin superfamily, can mediate intercellular adhesion by homophilic, Ca(2+)-independent binding. Immunohistochemical analysis of adult rat tissues has demonstrated that C-CAM is expressed in various epithelia, vessel endothelia, and hematopoietic cells. By molecular cloning and sequence analysis several isoforms differing both in the extracellular and the cytoplasmic domains have been found. Here we have analyzed the expression of C-CAM in the developing rat central nervous system. No neuronal expression was observed, but biochemical and immunohistochemical analyses demonstrated that C-CAM becomes expressed in the microvessels from embryonic day E-13; the intensity of the staining increased through day E-15 and then gradually decreased during the perinatal and early postnatal period. The expression of C-CAM in the walls of the microvessels was confirmed by in situ hybridization. Immunoelectron microscopy showed that C-CAM was localized both to the abluminal surface of the endothelial cells and to cellular processes of primordial pericytes where these two cell types are in contact with each other. No staining was found on the luminal endothelial cell surfaces or inter-endothelial cell contact areas. During the perinatal period C-CAM also became expressed on the opposite side of the pericytes and on other cells, possibly astrocytes, in contact with these areas of the pericytes. These observations suggest that C-CAM may be involved in heterotypic, homophilic adhesion between endothelial cells, pericytes and astrocytes, and in maturation of the vessel walls.

Journal of Cell …, 2001

Hemidesmosomes are multimeric protein complexes that attach epithelial cells to their underlying ... more Hemidesmosomes are multimeric protein complexes that attach epithelial cells to their underlying matrix and serve as cell surface anchorage sites for the keratin cytoskeleton. Two hemidesmosome components, the α6β4 integrin heterodimer and a human autoantigen termed BP180, are ...

The …, 2006

BACKGROUND. Connexins have their traditional function as part of gap junction (GJ) structures, bu... more BACKGROUND. Connexins have their traditional function as part of gap junction (GJ) structures, but have recently been shown to have GJ-independent roles. Although GJs and their connexin subunits are thought to be down-regulated in cancer, depending on the connexin examined, many times the expression level is preserved or even increased. This is further apparent by the importance of GJs in ''by-stander effects'' of radiation and viral targeting treatments. METHODS. We surveyed connexin isoforms in prostate cancer cell lines and tissue with RT-PCR and immunohistochemistry. Upon modulating GJ function, we observed prostate epithelial cell behaviors. RESULTS. Advanced cells within PC-3 and LNCaP prostate cancer progression models exhibit elevated connexin 26 (Cx26) levels-a trend validated in clinical samples. When GJs were inhibited, adhesion was not affected, but invasion and migration were strikingly decreased. A link between the expression of Cx26 and integrin adhesion-linked functions are suggested by Cx26's direct interaction with focal adhesion kinase (FAK). CONCLUSIONS. These results suggest a novel mechanism for adhesion regulation by a GJindependent Cx26 function that correlates with prostate disease progression. The increased Cx26 expression during prostate cancer progression plays a role in adhesion regulation possibly through its interaction with FAK.

Cell Growth Differentiation the Molecular Biology Journal of the American Association For Cancer Research, Feb 1, 2001

During prostate cancer progression, invasive glandular epithelial cells move out of the ductal-ac... more During prostate cancer progression, invasive glandular epithelial cells move out of the ductal-acinar architecture and through the surrounding basement membrane. Extracellular matrix proteins and associated soluble factors in the basal lamina and underlying stroma are known to be important regulators of prostate cell behaviors in both normal and malignant tissues. In this study, we assessed cell interactions with extracellular matrix and stromal factors during disease progression by characterizing integrin usage and expression in a series of parental and lineage-derived LNCaP human prostate cancer cell lines. Although few shifts in integrin expression were found to accompany disease progression, integrin heterodimer usage did change significantly. The more metastatic sublines were distinct in their use of ␣ v ␤ 3 and, when compared with parental LNCaP cells, showed a shift in ␣ 6 heterodimerization, a subunit critical not only for interaction with prostate basal lamina but also for interaction with the bone matrix, a favored site of prostate cancer metastases.

Cell Motility and the Cytoskeleton, 2001

Motile cells undergo changes in cell adhesion, behavior, and shape that are mediated by small-sca... more Motile cells undergo changes in cell adhesion, behavior, and shape that are mediated by small-scale cytoskeletal rearrangements. These rearrangements have proven difficult to follow quantitatively in living cells, without disrupting the very structures and delicate protein ...

Current Biology, May 15, 2000

Advances in cancer research, 2004

Clinical Genitourinary Cancer, 2006

Copyright information:Taken from "Met-Independent Hepatocyte Growth Facto... more Copyright information:Taken from "Met-Independent Hepatocyte Growth Factor-mediated regulation of cell adhesion in human prostate cancer cells"BMC Cancer 2006;6():197-197.Published online 25 Jul 2006PMCID:PMC1559714. (A) Met was precipitated in the PC3 cell line, while (B) in the C4-2 cell line two bands were precipitated using HGF coated beads but not with BSA control beads. The lower major band is HGF itself; the upper 100 kDa band was purified and sequenced. Western-blot analyses (C) and sequencing of the upper band confirmed it to be nucleolin (see table 2). (D) The importance of nucleolin to HGF-stimulated spreading on laminin substrata was apparent when antibodies to nucleolin reduced the effect of HGF (E). The cell spreading behaviors were quantified and presented as the mean of triplicate experiments. Statistically significant differences from the control were at P =< 0.005 (*).

Copyright information:Taken from "Met-Independent Hepatocyte Growth Facto... more Copyright information:Taken from "Met-Independent Hepatocyte Growth Factor-mediated regulation of cell adhesion in human prostate cancer cells"BMC Cancer 2006;6():197-197.Published online 25 Jul 2006PMCID:PMC1559714. (A) All cell lines, except LNCaP, increased cell spreading on laminin, following exposure to the SCM. (B) C4-2 cell attachment to laminin, following treatment with SCM or purified HGF. Cells were allowed to attach for 90 min., at which point ~25% of untreated C4-2 cells showed membrane protrusions. Induction of cell spreading, as seen for both SCM and purified HGF, is reversible by addition of anti-HGF antibody. Conditioned media from three primary stromal cell lines gave similar results (data not shown). Experimental cell spreading is shown as a percentage of control, untreated cells. Statistically significant differences from the control in each group were below P =< 0.05 (*). For each data point n = 6 or more.

International Journal of Cancer, 2004

Journal of Biological Chemistry, 1996

Molecular Biology of the Cell, 2004

Developmental Brain Research, 1994

Journal of Cell …, 2001

The …, 2006

Cell Growth Differentiation the Molecular Biology Journal of the American Association For Cancer Research, Feb 1, 2001

Cell Motility and the Cytoskeleton, 2001