Anti-CD6 Monoclonal antibody, clone JN459

Background: Activated leucocyte cell adhesion molecule (ALCAM, CD166) is a cell surface member of the immunoglobulin superfamily. ALCAM expression has prognostic relevance in prostate and colon cancer. Objective: To evaluate ALCAM protein expression in breast cancer by immunohistochemistry and to correlate expression levels with clinicopathological data. Methods: 162 primary breast carcinomas with a mean clinical follow up time of 53 months were immunostained using a monoclonal ALCAM antibody. The staining was evaluated as an immunoreactive score (IRS) and grouped into low v high for both membranous and cytoplasmic staining. Results: Intraductal and invasive carcinomas showed a higher ALCAM expression (median IRS 4 and 6 respectively) than normal breast tissue (IRS 2). In univariate survival analyses a significant association of high cytoplasmic ALCAM expression with shortened patient disease-free survival (mean (SD) five year non-progression rate, 69.4 (4.6)% v 49.4 (11.1)%, p=0.0142) was found. In multivariate analyses of disease-free survival times, high cytoplasmic ALCAM expression (relative risk (RR)=2.086, p=0.026) and nodal status (RR=2.246, p=0.035) were significantly associated with earlier disease progression, whereas tumour grading (RR=1.6, p=0.052) was of borderline significance. Conclusions: The data suggest that strong cytoplasmic ALCAM expression in primary breast cancer, as detected by immunohistochemistry, might be a new marker for a more aggressive breast cancer biology.

The plant cell wall is the barrier that pathogens must overcome to cause a disease, and to this end they secrete enzymes that degrade the various cell wall components. Due to the complexity of these components, several types of oligosaccharide fragments may be released during pathogenesis and some of these can act as damage-associated molecular patterns (DAMPs). Well-known DAMPs are the oligogalacturonides (OGs) released upon degradation of homogalacturonan and the products of cellulose breakdown, i.e. the cellodextrins (CDs). We have previously reported that four Arabidopsis berberine bridge enzyme-like (BBE-like) proteins (OGOX1-4) oxidize OGs and impair their elicitor activity. We show here that another Arabidopsis BBE-like protein, which is expressed coordinately with OGOX1 during immunity, specifically oxidizes CDs with a preference for cellotriose (CD3) and longer fragments (CD4-CD6). Oxidized CDs show a negligible elicitor activity and are less easily utilized as a carbon source by the fungus Botrytis cinerea. The enzyme, named CELLOX (cellodextrin oxidase), is encoded by the gene At4g20860. Plants overexpressing CELLOX display an enhanced resistance to B. cinerea, probably because oxidized CDs are a less valuable carbon source. Thus, the capacity to oxidize and impair the biological activity of cell wall-derived oligosaccharides seems to be a general trait of the family of BBE-like proteins, which may serve to homeostatically control the level of DAMPs to prevent their hyperaccumulation. Significance Statement This paper uncovers the activity of a member of the gene family encoding the berberine bridge enzyme-like (BBE-like) proteins. It encodes a specific oxidase that impairs the damage-associated molecular pattern (DAMP) activity of cellodextrins and plays a role in immunity. The oxidation and inactivation of DAMPs seem to be general and important functions of several BBE-like proteins and this work opens up avenues for the study of the physiological role and evolution of this family.