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Biomedical subjects

G D Steele

Publications and source records attributed to G D Steele.

At least 37 records · Page 2Linked to original sources
PubMed1993

Localization of tumor-associated glycoprotein DF3 in normal, inflammatory, and neoplastic lesions of the colon.

BACKGROUND: The expression of DF3 was assessed by a monoclonal antibody in normal, inflammatory, and neoplastic conditions in the large bowel. METHODS: Using immunohistochemistry, expression was examined in formalin-fixed paraffin-embedded biopsy and resection samples of 19 normal colonic mucosal specimens, 49 inflammatory lesions, 34 adenomas, and 38 primary colonic adenocarcinomas. In addition, Western blots of normal colonic mucosa and adenocarcinoma were examined. RESULTS: DF3 expression was detected in 84% of the adenocarcinomas with coarse membrane staining, intense positivity of luminal secretions, and focal cytoplasmic and intracytoplasmic vacuole staining. Nine of 32 areas of transitional mucosa revealed reactivity along apical membranes in crypt cells. Five adenomas containing carcinoma revealed DF3 positivity in the malignant areas only, whereas the remaining 29 were negative. Staining was membrane, luminal, and intracytoplasmic. Two examples of active ulcerative colitis revealed focal reactivity along the apical membrane of crypt cells. No other areas of staining were noted, including 12 cases containing dysplasia. Four of 10 other inflammatory lesions also revealed similar membrane reactivity in crypt cells. Normal colonic mucosa was nonreactive. Examples of normal colonic mucosa were negative for DF3 by Western blot analysis, whereas two carcinoma samples that reacted immunohistochemically were positive. CONCLUSIONS: DF3 is not detectable in normal colonic tissues. It is expressed focally and predominantly along the apical membrane of crypt cells in some inflammatory lesions and in the transitional mucosa of primary adenocarcinomas. Most adenocarcinomas of the colon and adenomas with foci of invasive carcinoma demonstrate reactivity in the cytoplasm and luminal secretions.

Adenocarcinoma↗
PubMed1993

Preoperative and postoperative combination chemotherapy for potentially resectable gastric carcinoma.

BACKGROUND: Median survival of patients with local-regional gastric carcinoma is 10 months. Resection of the primary tumor and regional lymph nodes, with tumor-free margins (curative resection), has been the most effective treatment for local-regional gastric carcinoma. However, median survival of patients with curative resection of gastric carcinoma is 24 months, and the 5-year survival rate is about 20%. A single institution pilot study has established the feasibility of administering two courses of chemotherapy preoperatively and three courses postoperatively. In another study, a 15% pathologically documented complete response (pathologic complete response) has been reported in unresectable gastric carcinoma treated with etoposide, doxorubicin, and cisplatin. PURPOSE: Our purpose was to increase the curative resection rate in potentially resectable gastric carcinoma and to delay or eliminate micrometastases and thus improve survival. We also evaluated clinical and pathologic response to chemotherapy. METHODS: Forty-eight previously untreated patients with potentially resectable gastric carcinoma received a chemotherapy regimen (EAP) consisting of etoposide (120 mg/m2 intravenously over a 2-hour period on days 4, 5, and 6), doxorubicin (20 mg/m2 as a 10-minute intravenous infusion on days 1 and 7), and cisplatin (40 mg/m2 as a 1-hour intravenous infusion on days 2 and 8). Patients received three courses of chemotherapy before resection, and responding patients received two courses postoperatively. Clinical and pathologic response rates, toxicity, patterns of treatment failure, and survival times were assessed. RESULTS: A median of three courses (range, 1-5) of preoperative therapy was administered; six (12%) of the 48 patients had clinical complete response, and nine (19%) had partial response. Forty-one (85%) underwent surgery; 37 (90%) of these 41 (77% of the 48 patients) had a curative resection. There were no pathologic complete responses. Median survival for all patients is 15.5 months (range, 2-29+ months). Therapy was discontinued because of the toxic effects in one patient before surgery and in six patients after surgery. Doses were reduced in 37 patients (77%), mainly because of hematologic toxicity. Nineteen (40%) were hospitalized because of toxic effects, including 15 patients who developed fever with neutropenia. Grade 3 or 4 nausea and vomiting occurred in 15 patients and grade 3 or 4 diarrhea in seven patients. One death was directly related to chemotherapy. CONCLUSIONS: These data support that administration of preoperative and postoperative chemotherapy for local-regional gastric carcinoma is feasible in a multi-institutional setting. Our findings demonstrate that this EAP regimen is modestly active but is associated with substantial toxicity. IMPLICATIONS: Use of preoperative chemotherapy in resectable gastric carcinoma merits further evaluation, but more effective drug regimens will be required before a controlled trial is initiated.

Adenocarcinoma↗
PubMed1993

Nucleotide and deduced amino acid sequence of human ribosomal protein L18.

Ribosomal protein L18 mRNA is overexpressed in human colorectal cancer compared to normal colon tissue. We report the nucleotide sequence of human L18 cDNA derived from a normal colon source. There were no mutational changes in segments of L18 cDNA derived from two tumor sources. The L18 cDNA was 690 base pairs long and predicts a single open reading frame of 564 nucleotides, encoding 188 amino acids with a M(r) = 21,621, it is homologous to rat L18 and Xenopus laevis L14.

Amino Acid Sequence↗
PubMed1993

Gastric and hepatocellular carcinomas do not overexpress the same ribosomal protein messenger RNAs as colonic carcinoma.

The levels of a number of ribosomal protein mRNAs are reported to be increased in human colon cancer. We have assessed whether selected ribosomal protein mRNAs are overexpressed in other gastrointestinal malignancies, namely gastric and hepatocellular carcinomas. Subtracted complementary DNA libraries were generated from paired samples of human (a) colorectal carcinoma minus adjacent normal colonic mucosa and (b) hepatocellular carcinoma minus adjacent normal liver. Screening of approximately 3% of these library clones determined that ribosomal protein mRNAs encoding L18 and L37 (not previously reported) and P0 and S6 were overexpressed in one or the other library. Their complementary DNA inserts were then used as probes to evaluate their expression in a larger number of paired tumor/normal surgical samples of human colonic, gastric, and hepatocellular carcinomas, by Northern hybridization. The mRNA signal was greater in the colonic carcinoma than in paired adjacent normal colonic mucosa in 38 of 42 cases for P0 [tumor/normal (T/N) ratio = 3.0 +/- 0.3, mean +/- SE, P < 0.001] (G. F. Barnard, R. J. Staniunas, S. Bao, K. Mafune, J. L. Gollan, G. D. Steele, Jr., and L. B. Chen, Cancer Res., 52: 3067-3072, 1992), in 25 of 28 cases for L18 (T/N ratio = 3.7 +/- 0.5, P < 0.001), in 27 of 28 cases for L37 (T/N ratio = 5.3 +/- 0.4, P < 0.001), and in 24 of 28 cases for S6 (T/N ratio = 3.1 +/- 0.5, P < 0.01). The level of mRNA overexpression of L18 and S6 did not correlate with the Dukes' stage of disease. In hepatocellular carcinoma samples, using the same four ribosomal protein complementary DNA probes, only P0 mRNA was significantly increased (T/N ratio = 2.8 +/- 0.4, n = 6, P = 0.047). In gastric carcinoma samples, none of these mRNAs was increased (mean T/N ratios = 0.9-1.2, n = 6). Therefore, gastric and hepatocellular carcinomas do not overexpress the same ribosomal protein mRNAs as do colonic carcinoma.

Base Sequence↗
PubMed1993

Modulation of mdr-1 expression by a H-ras oncogene in a human colon carcinoma cell line.

In an established colon differentiation model, introduction of a c-H-ras-1 oncogene into a poorly differentiated human colon carcinoma cell line (Clone A) results in changes associated with the acquisition of a more differentiated phenotype. Down-regulation of mdr-1 mRNA was shown to accompany ras-related differentiation events resulting in decreased Pgp synthesis and a significant reduction in membrane Pgp as detected by immunoprecipitation, Western-blot and FACS analysis. Consistent with these observations was a reduction in Pgp-mediated drug resistance associated with Clone-A ras transfectants, with no alteration in drug sensitivity being observed with non-MDR drugs in these cells. An alternative differentiation model involves exposure of Clone-A cells to sodium butyrate. Under these conditions, differentiation-related changes resulted in up-regulation of mdr-1 mRNA and Pgp synthesis, although no alteration in drug sensitivity was recorded. In agreement with this observation, the levels of membrane-associated Pgp remained unchanged throughout the period of exposure to sodium butyrate. This study shows that modulation of Pgp expression in colon differentiation is dependent upon the differentiation induction agent used.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Decreased expression of Mac-2 (carbohydrate binding protein 35) and loss of its nuclear localization are associated with the neoplastic progression of colon carcinoma.

The Mac-2 lectin (carbohydrate binding protein 35) is a soluble, 32- to 35-kDa phosphoprotein that binds galactose-containing glycoconjugates. We report here that the colonic epithelium is a major site of Mac-2 expression in vivo based on immunohistochemistry of human tissue specimens. In this epithelium, proliferating cells at the base of the crypts do not express Mac-2 but its expression increases with differentiation along the crypt-to-surface axis. Mac-2 expression is concentrated in the nuclei of these differentiated epithelial cells. The progression from normal mucosa to adenoma to carcinoma is associated with significant changes in Mac-2 nuclear localization and expression. In all adenomas (9/9) and carcinomas (13/13) examined, Mac-2 was not present in the nucleus but was localized in the cytoplasm. Sequencing of Mac-2 cDNAs from normal mucosa and carcinoma revealed no specific mutations that could account for this loss of nuclear localization. We also observed a 5- to 10-fold decrease in Mac-2 mRNA levels in cancer compared to normal mucosa as well as a significant reduction in the amount of Mac-2 protein expressed. These observations suggest that Mac-2 exclusion from the nucleus and its decreased expression may be related to the neoplastic progression of colon cancer.

Adenocarcinoma↗
PubMed1993

Ubiquitin-ribosomal protein S27a gene overexpressed in human colorectal carcinoma is an early growth response gene.

One of the extension proteins on the carboxy terminus of ubiquitin was reported as the ribosomal protein S27a. We have cloned a gene which encodes this ubiquitin hybrid protein from a complementary DNA library of a human colon carcinoma cell line. Northern blot analysis of surgical specimens from colon cancer patients showed that these messenger RNA levels were higher in tumor tissue than in adjacent normal mucosa. Furthermore, to investigate the role of this novel ubiquitin hybrid gene in cellular growth control, the responsiveness of this gene to serum growth factors was examined. Within 30 min after serum or 12-O-tetradecanoylphorbol-13-acetate stimulation, its messenger RNA expression in rat fibroblast cells (Rat 1) was increased. Nuclear runoff transcription studies showed that the kinetics of induction of this gene is almost identical to that of protooncogene c-jun or c-fos, the known early growth response genes. Thus, this ubiquitin hybrid gene appears to be a novel early growth response gene overexpressed in human colon cancer and warrants further studies in the pathogenesis of colorectal carcinoma.

Animals↗
PubMed1993

Human and murine Kupffer cell function may be altered by both intrahepatic and intrasplenic tumor deposits.

The liver is the most common site of hematogenous metastases from colorectal carcinoma. Kupffer cells (KC), which line the hepatic sinusoids, may form the first line of defense against circulating tumor cells. The purpose of this study was to determine the effect of hepatic metastases and intra-abdominal tumor growth on KC binding of human colorectal carcinoma (HCRC) cells. MIP-101, a poorly metastatic cell line, and CX-1, a highly metastatic cell line, were injected intrasplenically into nude mice and KC were isolated by collagenase perfusion at varying intervals after injection. Conditioned media were collected from MIP-101, CCL 188 and CX-1 to determine their in vitro effect on KC function. KC from MIP-101 injected mice (14% liver metastases, 100% splenic tumors) bound a significantly greater number of MIP-101 and clone A cells than CX-1 cells in vitro. KC isolated from mice 5 weeks after CX-1 injection (100% liver metastases) also showed increased binding of MIP-101 and clone A cells compared to CX-1 cells. Similar results were obtained when tumor cell binding to normal human liver KC was compared to binding to KC from human livers from patients with hepatic metastasis from colorectal cancer. In contrast KC obtained from mice 3 weeks after CX-1 injection (44% liver metastases) showed significantly decreased binding of MIP-101 and clone A cells. The conditioned medium from CX-1 cells significantly decreased the in vitro binding of both MIP-101 and CX-1 by KC. These results indicate that the ability of KC to bind HCRC cells (which precedes phagocytosis and tumor cell killing) is a dynamic function and affected by concomitant tumor growth. HCRC cells may alter KC function via the production of specific tumor-derived soluble factors. In order to devise new and more effective therapeutic options in the treatment of liver metastases the nature of this tumor cell-KC interaction must be better understood.

Animals↗
PubMed1993

The significance of carbonic anhydrase expression in human colorectal cancer.

BACKGROUND: Carbonic anhydrase isoenzymes I and II are present in normal colorectal mucosa. This study aimed to determine if carbonic anhydrase is present in colorectal cancer and what is its potential clinical significance. METHODS: The messenger RNA (mRNA) and protein expression of carbonic anhydrase isoenzyme I were analyzed in fresh specimens of colorectal adenocarcinoma by Northern and Western blots, respectively. The immunohistochemical expression was subsequently studied in a larger number of formalin-fixed surgical specimens. RESULTS: All of 30 normal colon samples had a strong RNA hybridization signal. Only 4 of 39 paired colorectal cancer and none of 9 normal liver samples had detectable levels of carbonic anhydrase mRNA. Isoenzyme I protein expression showed similar results. In a separate group of patients, immunohistochemical studies showed that 16 of 96 colorectal tumors had positive staining cells. All positive tumors were well or moderately differentiated carcinomas (P < 0.05). When analyzed retrospectively, immunoreactive cases were more likely to be in a group with a good outcome (P < 0.01) and to lack vascular invasion (P < 0.01) than negative cases. CONCLUSIONS: The majority of colorectal cancers do not express carbonic anhydrase isoenzyme I. The presence of any isoenzyme I-positive immunoreactive cancer cells may be associated with a more favorable outcome in colorectal cancer.

Adult↗
PubMed1993

The prognostic significance of proliferating cell nuclear antigen in clinical gastric cancer.

BACKGROUND: Proliferating cell nuclear antigen (PCNA) is an intranuclear protein that is closely linked to the cell cycle. This antigen can be detected in formalin-fixed specimens. We studied the expression of PCNA in primary gastric cancer to identify its significance as a prognostic factor. METHODS: The avidin-biotin-peroxidase complex method was used for PCNA staining in sections from 138 patients with primary gastric cancer. All sections were formalin fixed and paraffin embedded. Two different sections were examined in each case. RESULTS: The PCNA labeling index (PCNA-positive cells/1000 cells x 100) varied from 7.0% to 59.7%. There were significant differences in tumor size, morphologic type, depth of tumor invasion, lymphatic permeation, vascular permeation, and lymph node metastasis between the high (> or = 33.4) and low (< 33.4) PCNA labeling index groups. The 5-year survival rates of the high and low PCNA labeling index groups were 5.8% and 66.2%, respectively, a significant difference (p < 0.001). Multivariate analysis showed that the PCNA labeling index was an independent prognostic factor for gastric cancer. CONCLUSIONS: Because PCNA immunostaining can be done in routine formalin-fixed paraffin-embedded sections, this could be a powerful tool for providing information about the prognosis of patients with gastric cancer.

Antigens, Neoplasm↗
PubMed1993

Prothymosin-alpha mRNA expression correlates with that of c-myc in human colon cancer.

Prothymosin alpha (PT-alpha) is a nuclear protein involved in cell proliferation. Transcription of PT-alpha has been reported to be regulated by the c-myc gene in vitro. We identified PT-alpha as being overexpressed in a human colon cancer minus normal mucosa subtraction cDNA library. Northern blot (messenger RNA) analysis showed that both PT-alpha and c-myc genes were overexpressed in human colorectal cancers compared with adjacent normal tissues. Immunohistochemical studies for PT-alpha and c-myc supported these findings. There was no correlation between PT-alpha or c-myc messenger RNA expression and Dukes' stage of colorectal cancer; or between either of these two and actin messenger RNA expression. There was, however, a significant correlation between the PT-alpha expression and c-myc expression (P < 0.001). These findings support the hypothesis that PT-alpha gene transcription may be associated with, and possibly under the control of, the c-myc gene in human colorectal cancers.

Blotting, Northern↗
PubMed1992

Increased expression of human ribosomal phosphoprotein P0 messenger RNA in hepatocellular carcinoma and colon carcinoma.

To search for differentially expressed gene products in selected cancers of endodermal origin, cDNA libraries derived from mRNA in human hepatocellular carcinoma and adjacent grossly normal tissue were generated. From these parent libraries, subtracted cDNA libraries of tumor minus normal and normal minus tumor tissues were constructed. After screening these subtracted libraries by +/- hybridization, a cDNA clone that is overexpressed in hepatocellular carcinoma and encodes the human acidic ribosomal phosphoprotein P0 (P0) was identified. We then evaluated the expression of this phosphoprotein P0 in human colon carcinoma samples. Surgical specimens of primary tumors and liver metastases were examined by Northern hybridization of total RNA with one of 2 32P-labeled P0 probes. The mRNA level of the P0 was greater in primary colon carcinoma than in paired adjacent normal colonic epithelium in 36 of 38 cases; the mean tumor/normal ratio was 2.7 (range, up to 13). The tumor/normal ratio, when plotted against the Dukes' stage of disease, gave evidence for increasing P0 expression with increasing stage of colon carcinoma (P = 0.02). In all 8 cases of paired colon carcinoma metastatic to liver and 2 cases of paired primary hepatocellular carcinoma, the P0 mRNA level was greater in tumor than in adjacent normal liver tissue. The mean tumor/normal ratio was 4.0 (range, up to 11) for the colon cancers metastatic to liver and 4.2 for the primary hepatocellular carcinoma samples. These findings support a common increased expression of selected gene products in different tumors of endodermal origin and suggest that increased P0 expression, in line with certain other ribosomal proteins, may be associated with human colorectal cancer progression and biological aggressiveness.

Blotting, Northern↗
PubMed1992

Sialyltransferase activity and hepatic tumor growth in a nude mouse model of colorectal cancer metastases.

Sialyltransferase activity (EC 2.4.99.6) was measured in the microsomal fraction of colorectal cancer cell lines using an assay based on the incorporation of [14C]CMP-sialic acid into asialofetuin. In the poorly differentiated lines MIP101 and Clone A, sialyltransferase activity had a Vmax of 0.36 and 0.31 nmol/mg protein/h, respectively, while the moderately differentiated to well-differentiated cell lines HT-29, CCL188, and CX-1 had Vmaxs of 2.46, 1.05, and 1.24 nmol/mg protein/h, respectively. All cell lines tested had a Km of 15.4 (+/- 0.7)(SD) mumol/liter. The better differentiated cells had higher levels of sialyltransferase activity, which correlated with their higher levels of sialic acid and their enhanced ability to form liver metastases in the nude mouse following intrasplenic injection compared to the poorly differentiated cell lines. Treatment of the cell lines with KI-8110, a CMP-sialic acid derivative which prevents incorporation of sialic acid into glycoconjugates, resulted in reduced formation of hepatic metastases by the colorectal carcinoma cell lines in the nude mouse model. It is suggested that reduced sialylation of adhesion molecules such as carcinoembryonic antigen may change the biology of the tumor cell, one consequence of which is the prevention of implantation of the cells into distant sites, resulting in a reduced incidence of metastases.

Animals↗
PubMed1992

Technical and biological factors in disease-free survival after hepatic resection for colorectal cancer metastases.

Careful patient selection for hepatic resection of colorectal cancer metastases is essential to improve current poor results. Carcinoembryonic antigen level and number of metastases were significant preoperative prognostic indicators of 5-year disease-free survival in patients selected clinically for hepatic surgery. Surgical margin, weight of hepatic tissue resected, carcinoembryonic antigen level, and flow cytometry were significant postoperative prognostic indicators. Patients with a carcinoembryonic antigen level less than 200 ng/mL, 1-cm surgical margins, and less than 1,000 g of liver tissue removed had a greater than 50% estimated 5-year disease-free survival rate. If the metastases were diploid on flow cytometry, an additional survival advantage may have been gained. Inadequate surgical margins led to high rates of liver-only recurrence. Nonhepatic recurrence was unrelated to surgical margins. Intraoperative liver examination by ultrasound during primary colon cancer resection and adjuvant chemotherapy may offer earlier selection of biologically appropriate patients and improved outcome; both recommendations require clinical trials.

Adult↗
PubMed1992

Metastatic potential of human colon cancer cell lines: relationship to cellular differentiation and carcinoembryonic antigen production.

The relationship between cellular differentiation and carcinoembryonic antigen (CEA) production by human colorectal tumor cells and their ability to form hepatic metastases was studied. Eight human colon cancer cell lines were injected into athymic mice using different routes of administration to characterize their metastatic potential. The four poorly differentiated, non or low CEA producing cell lines were poorly metastatic to the liver after intrasplenic injection. After intraperitoneal implantation the same cell lines were highly tumorigenic, and subsequently metastatic to the liver. In contrast, the four moderate to well-differentiated cell lines that produced moderate to high levels of CEA were highly metastatic to the liver following intrasplenic injection. After intraperitoneal implantation they were less tumorigenic, and metastatic to the liver. We conclude that in this system poorly differentiated non or low CEA producing colorectal cell lines have a lower metastatic capacity compared to the well-differentiated high CEA producing colorectal cell lines. These data correlate directly with the pattern of metastatic spread and clinical course observed in patients with these tumors, suggesting that degree of differentiation and level of CEA production may play a role in development of site-specific metastases.

Animals↗
PubMed1992

Sucrase-isomaltase expression in chronic ulcerative colitis and dysplasia.

Sucrase-isomaltase (SI) is a mucosal disaccharidase that is present in normal small intestine and fetal colon. It also has been noted in colonic adenomas and adenocarcinomas. We used a polyclonal antibody to human SI to investigate enzyme presence and utility in detecting dysplastic changes in chronic ulcerative colitis. Sections from 32 cases were reviewed for the presence or absence of active colitis and dysplasia. Immunostaining of these cases for SI was performed and the results were reported based on location of immunoreactivity (ie, membrane and cytoplasmic staining in superficial and crypt epithelial cells) and percentage of positivity. Of 81 sections examined, 48 were rated negative for dysplasia (23 inactive colitis, 20 active, and five probably negative) and 28 were rated positive (eight low grade and 20 high grade). Surface membrane staining of epithelial cells was noted in all 28 dysplastic slides and positive cases (sensitivity, 100%) but also in 29 of 48 negative sections (P less than .001). In contrast, cytoplasmic positivity was present in 25 of 28 dysplastic and in only two of 48 negative slides (P less than .0001). The presence of cytoplasmic staining of SI in the superficial or crypt cells revealed a sensitivity of 92% and a specificity of 94%. There were five additional sections rated as indefinite for dysplasia (probably positive or unknown); two showed staining patterns typical of negative slides and three showed positive staining patterns. Of the 18 samples of transitional mucosa next to areas of dysplasia, surface membrane staining of SI was seen in all samples and cytoplasmic staining was seen in 15. We conclude that membrane staining of SI can be detected in inflammatory, regenerative, and dysplastic mucosa in ulcerative colitis. Cytoplasmic staining, however, correlates strongly with the presence of dysplastic change and may help in its detection.

Adult↗
PubMed1992

The integrin alpha 6 beta 4 is a laminin receptor.

In this study, the putative laminin receptor function of the alpha 6 beta 4 integrin was assessed. For this purpose, we used a human cell line, referred to as clone A, that was derived from a highly invasive, colon adenocarcinoma. This cell line, which expresses the alpha 6 beta 4 integrin, adheres to the E8 and not to the P1 fragment of laminin. The adhesion of clone A cells to laminin is extremely rapid with half-maximal adhesion observed at 5 min after plating. Adhesion to laminin is blocked by GoH3, and alpha 6 specific antibody (60% inhibition), as well as by A9, a beta 4 specific antibody (30% inhibition). Most importantly, we demonstrate that alpha 6 beta 4 binds specifically to laminin-Sepharose columns in the presence of either Mg2+ or Mn2+ and it is eluted from these columns with EDTA but not with NaCl. The alpha 6 beta 4 integrin does not bind to collagen-Sepharose, but the alpha 2 beta 1 integrin does bind. Clone A cells do not express alpha 6 beta 1 as evidenced by the following observations: (a) no beta 1 integrin is detected in beta 1 immunoblots of GoH3 immunoprecipitates; and (b) no alpha 6 beta 1 integrin is seen in GoH3 immunoprecipitates of clone A extracts that had been immunodepleted of all beta 4 containing integrin using the A9 antibody. These data establish that laminin is a ligand for the alpha 6 beta 4 integrin and that this integrin can function as a laminin receptor independently of alpha 6 beta 1.

Adenocarcinoma↗