The cellular and molecular interaction between tumor cells and platelets - role in diagnosis and tumor metastasis.

Early identification of carcinogenesis and prevention of metastasis are two
important clinical challenges for gastrointestinal tumors. The role of blood
platelets in these processes is gaining interest. It has been shown that
platelet activation state and platelet mRNA profiles in breast cancer patients
are significantly altred as compared to healthy controls, and studies are
ongoing to investigate whether such tumor-education of platelets may be used
for early identification of patients with breast cancer. In addition to tumor
cell modulation of platelets, it has also been suggested that platelets can
modulate tumor cells. Coating of tumor cells with platelets facilitates their
migration, allows their escape from immunosurveillence by NK cells, amongst
others by inducing shedding of NKG2D ligands from tumor cells. We have
previously shown that several phosphatases (e.g. LMWPTP, PTP1B) are
overexpressed in colorectal, prostate and haematological malignancies and
confer cancer hallmarks. We have shown that LMPWTP decreases survival and
promotes metastasis, and demonstrated in vitro that overexpression of this
phosphatase affects tumor cell migration. Our preliminary data further suggest
that platelets show increased interaction with tumor cells which express high
levels of LMWPTP or PTP1B, indicating an advantage for cells expressing these
phosphatases to metastasize. We have additionally shown that LMPWTP in
platelets is upregulated in response to agonists in healthy controls, and thus
may contribute to their reactivity and tumor education. To what extent
phosphatases plays a role in the tumor education of platelets (TEP), and
whether platelets from patients with gastrointestinal cancers show altered
tumor-activating properties, is as yet unknown.

1. To investigate tumor-interaction properties and tumor-education of platelets
from patients with GI cancers.
2. To expand our knowledge of phosphatase expressions pattern in GI cancers

1. Molecular and cellular analysis of platelet activation behaviour in relation
to LMWPTP and PTP1B expression will be studied by investigating platelet
activation markers, tumor education and LMWPTP/PTP1B expression. Patients with
esophageal, gastric, and colorectal cancer will be compared with eachother and
healthy controls. Furthermore we will in vitro incubate platelets from
patients with GI cancer and controls with tumor cell lines expressing high and
low levels of LMWPTP/PTP1B and assess platelet aggregation patterns as well as
molecular changes in both platelets and tumor cells.
2. FFPE sections of oesophageal and gastric cancer tissue as well as normal
squamous esopgeal tissue and gastric tissue will be stained for LMWPTP and
PTP1B expression. These tumors show high metastatic potential, and are
therefore expected to carry high levels of these phosphatases, as was
previously demonstrated for colorectal cancer.

Participants will be asked to donate blood (3 tubes) during routine clinical
visits. The burden and risk of this study is therefore negligible. FFPE
sections will be identified from the PALGA database, and no new biopsies are
required for this study. The study is expected to yield insight into tumor
metastasis biology, thrombosis risk and may provide support for diagnostic
cancer hallmarks in the form of tumor-educated platelets, which may help
predict patients at risk for metastasis in the future. Metastasis of disease
is particularly common in GI cancer, and is the major cause of death.
Prevention of metastasis is expected to contribute to improved patient
survival.