BACKGROUND. The a6b4 integrin and its ligand, laminin-5, are essential gene products for the maintenance and remodeling of a strati®ed epithelium. Apparent loss of polarized a6b4 integrin and laminin-5 protein expression in invasive prostate cancer as compared to normal prostate glands is known to occur. It is unknown whether these alterations occur in prostatic intraepithelial neoplasia (PIN) lesions and whether this combined defect occurs in other epithelial cancers. METHODS. Human prostate tissues containing both normal, PIN, and cancerous regions and normal and cancer tissue from breast and colon were obtained at surgery and examined for b4 integrin and laminin-5 using standard immuno¯uorescence staining methods. RESULTS. Both normal prostate glands and PIN lesions contain b4 integrin and laminin-5. Prostate carcinoma was unique in that both b4 integrin and laminin-5 expression was uniformly absent. In contrast, the b4 integrin and its ligand, laminin-5 were detected in all of the colon carcinoma cases and in 60% of the breast carcinomas. CONCLUSIONS. The b4 integrin and its ligand, laminin-5 are altered during the transition of PIN lesions to invasive prostate carcinoma. These data suggest the loss of these proteins during cancer progression. In both prostate and breast carcinoma, the normal expression pattern of the b4 integrin and laminin-5 is interrupted, in contrast to the persistent b4 integrin and laminin-5 expression detected in colon carcinoma. Prostate 46: 240±248, 2001. KEY WORDS:integrin; prostate; epithelial; laminin; carcinoma; a6b4; colon; breast; tissue INTRODUCTIONProstate cancer, the most common visceral neoplasm in males [1] is variable in its clinical progression. Many cases present with slow-growing, clinically inapparent forms of the invasive carcinoma con®ned to the prostate, while others present with a rapidly growing, aggressive tumor that quickly metastasizes. The cause of this variability is still unknown, but is due in part to differences in the ability of a given carcinoma for cellular invasion and metastatic spread.During invasion, tumor cells can make an extracellular matrix which differs from that found in the normal structures. The invading cells interact with the new basal lamina to promote migration [2,3]. Prostate carcinomas synthesize a new basal lamina lacking the b3 and g2 subchains of laminin-5 [4,5]. Colorectal carcinomas produce a laminin-5-rich basal lamina, the presence of which was correlated with a high degree of metastasis to the liver. These metastatic lesions often had intact, well-de®ned basal lamina [6]. Gastric carcinomas also have been shown to increase their expression of laminin-5 at the invasive edge [3,7]. Invasive prostate carcinoma also is associated with changes in cell adhesion receptors. In particular, loss of E-cadherin [8±11], gain of N-cadherin, loss of hemidesmosomes [4,12], and integrin alterations occur [10,13±17]. The a6b4 integrin which is expressed mainly in strati®ed epithelial tissues, is the predominant integrin pair found in normal pr...

The ␣ 6 integrin is a 140-kDa (nonreduced) laminin receptor. We have identified a novel 70-kDa (nonreduced) form of the ␣ 6 integrin called ␣ 6 p for the latin word parvus, meaning small. The variant was immunoprecipitated from human cells using four different ␣ 6 -specific monoclonal antibodies but not with ␣ 3 or ␣ 5 antibodies. The ␣ 6 p integrin contained identical amino acid sequences within exons 13-25, corresponding to the extracellular "stalk region" and the cytoplasmic tail of the ␣ 6 integrin. The light chains of ␣ 6 and ␣ 6 p were identical as judged by ␣ 6 Aspecific antibodies and electrophoretic properties. The ␣ 6 p variant paired with either ␤ 1 or ␤ 4 subunits and was retained on the cell surface three times longer than ␣ 6 . Reverse transcription/polymerase chain reaction analysis revealed a single polymerase chain reaction product. The ␣ 6 p variant was found in human prostate (DU145H, LnCaP, PC3) and colon (SW480) cancer cell lines but not in normal prostate (PrEC), breast cancer (MCF-7), or lung cancer (H69) cell lines or a variant of a prostate carcinoma cell line (PC3-N). Protein levels of ␣ 6 p increased 3-fold during calcium-induced terminal differentiation in a normal mouse keratinocyte model system. A novel form of the ␣ 6 integrin exists on cell surfaces that contains a dramatically altered extracellular domain.

Cutaneous collagenous vasculopathy (CCV) is an idiopathic microangiopathy involving the superficial blood vessels that was initially reported in a 54-year-old male. We recently have identified this rarely reported entity in three Caucasian males. The first patient was a 59-year-old male with diabetes, hypertension and hypercholesterolemia who presented with multiple, red, blanchable, asymptomatic telangiectasias covering the extensor surface of the forearms, the lower abdomen and parts of the chest. The second patient was a 62-year-old male with psoriasis and extensive arthritis who presented with prominent telangiectasias on the left lateral distal thigh with mild overlying epidermal atrophy. The third patient was an 80-year-old male with atrial fibrillation who presented with blanching, telangiectatic areas on the abdomen, thighs and back. Histologically, the skin lesions showed ectatic superficial small blood vessels with laminated, hyalinized concretions around vessels that were highlighted with periodic acid-Schiff staining following diastase digestion and reactive by immunohistochemical staining with an antibody to collagen type IV. CCV is a rare and poorly understood entity with distinct histopathological features that may clinically resemble generalized essential telangiectasia (GET), yet which may affect a different demographic population than GET. Awareness of this uncommon entity may further help to elucidate its etiology.

Fertility control is a potential method for managing overabundant wildlife populations; however, current technology is limited by duration of treatment efficacy and unacceptable side effects. The objective of this study was to determine the efficacy of a single immunization with gonadotropin-releasing hormone (GnRH) vaccine to suppress reproductive function in pregnant female elk and to evaluate potential behavioral and pathological side effects of treatment. Eighteen captive adult female elk were randomly allocated to one of two experimental groups. Ten females were administered a conjugated and adjuvanted GnRH vaccine intramuscularly, and eight elk received an adjuvant sham vaccine without conjugated GnRH. We compared success of existing pregnancy, neonatal survival, subsequent fertility, reproductive behavior rates, and side effects of treatment between January 2006 and January 2010. The GnRH vaccination did not affect existing pregnancy or calf survival during the year that it was applied; however, it reduced the proportion of pregnant females for 3 yr. Male precopulatory behavior rates exhibited toward GnRH-vaccinated females tended to be greater than those directed at sham-vaccinated females during the second half of the breeding season, when GnRH vaccinates continued to be proceptive. Strong immune and inflammatory responses, including robust GnRH antibody concentrations in GnRH vaccinates, and sterile pyogranulomatous injection site abscesses in both groups, were consistent with vaccination. In conclusion, this GnRH vaccine resulted in prolonged, albeit reversible, impairment of fertility, and is associated with extended reproductive behaviors and partial suppression of hypothalamic-pituitary-gonadal axis function in captive female elk.

Background The α6β4 integrin and its ligand, laminin‐5, are essential gene products for the maintenance and remodeling of a stratified epithelium. Apparent loss of polarized α6β4 integrin and laminin‐5 protein expression in invasive prostate cancer as compared to normal prostate glands is known to occur. It is unknown whether these alterations occur in prostatic intraepithelial neoplasia (PIN) lesions and whether this combined defect occurs in other epithelial cancers. Methods Human prostate tissues containing both normal, PIN, and cancerous regions and normal and cancer tissue from breast and colon were obtained at surgery and examined for β4 integrin and laminin‐5 using standard immunofluorescence staining methods. Results Both normal prostate glands and PIN lesions contain β4 integrin and laminin‐5. Prostate carcinoma was unique in that both β4 integrin and laminin‐5 expression was uniformly absent. In contrast, the β4 integrin and its ligand, laminin‐5 were detected in all of the colon carcinoma cases and in 60% of the breast carcinomas. Conclusions The β4 integrin and its ligand, laminin‐5 are altered during the transition of PIN lesions to invasive prostate carcinoma. These data suggest the loss of these proteins during cancer progression. In both prostate and breast carcinoma, the normal expression pattern of the β4 integrin and laminin‐5 is interrupted, in contrast to the persistent β4 integrin and laminin‐5 expression detected in colon carcinoma. Prostate 46:240–248, 2001. © 2001 Wiley‐Liss, Inc.